Descriptor: "MESH : Apoptosis" - Searchworks@Jio Institute Digital Library Search Results

Your search keyword '"MESH : Apoptosis"' showing total 73 results

Start Over Descriptor "MESH : Apoptosis"

73 results on '"MESH : Apoptosis"'

1. Patched dependence receptor triggers apoptosis through ubiquitination of caspase-9

Author: Patrick Mehlen, Chantal Thibert, Rémy Sadoul, Joanna Fombonne, Catherine Guix, Pierre-Antoine Bissey, Puisieux, Alain, Centre de Recherche en Cancérologie de Lyon (UNICANCER/CRCL), Centre Léon Bérard [Lyon]-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), INSERM U836, équipe 2, Neurodégénérescence et plasticité, Grenoble Institut des Neurosciences (GIN), Université Joseph Fourier - Grenoble 1 (UJF)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Joseph Fourier - Grenoble 1 (UJF)-Institut National de la Santé et de la Recherche Médicale (INSERM), This work was supported by institutional grants from the Ligue Contre le Cancer, INCA, ANR, and IP ApoSys., Institute for Advanced Biosciences / Institut pour l'Avancée des Biosciences (Grenoble) (IAB), Centre Hospitalier Universitaire [Grenoble] (CHU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Etablissement français du sang - Auvergne-Rhône-Alpes (EFS)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019]), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre de Recherche en Cancérologie de Lyon ( CRCL ), Centre Léon Bérard [Lyon]-Université Claude Bernard Lyon 1 ( UCBL ), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ), Grenoble Institut des Neurosciences ( GIN ), and Université Joseph Fourier - Grenoble 1 ( UJF ) -CHU Grenoble-Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Université Joseph Fourier - Grenoble 1 ( UJF ) -CHU Grenoble-Institut National de la Santé et de la Recherche Médicale ( INSERM )
Subjects: MESH : Cell Line, endocrine system diseases, Apoptosis, NEDD4, [SDV.BC.BC]Life Sciences [q-bio]/Cellular Biology/Subcellular Processes [q-bio.SC], Dependence receptor, MESH : Ubiquitination, 0302 clinical medicine, Ubiquitin, [SDV.BC.IC]Life Sciences [q-bio]/Cellular Biology/Cell Behavior [q-bio.CB], MESH: Caspase 3, MESH : Caspase 3, ComputingMilieux_MISCELLANEOUS, Caspase-9, 0303 health sciences, Multidisciplinary, biology, Caspase 3, MESH: Real-Time Polymerase Chain Reaction, Signal transducing adaptor protein, Biological Sciences, MESH : Mutagenesis, Site-Directed, Ubiquitin ligase, MESH: Mutagenesis, Site-Directed, 030220 oncology & carcinogenesis, Patched, MESH : Real-Time Polymerase Chain Reaction, [SDV.CAN]Life Sciences [q-bio]/Cancer, macromolecular substances, Real-Time Polymerase Chain Reaction, MESH: Two-Hybrid System Techniques, Cell Line, 03 medical and health sciences, Two-Hybrid System Techniques, signalisation, [SDV.BBM] Life Sciences [q-bio]/Biochemistry, Molecular Biology, Humans, [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology, [ SDV.BBM ] Life Sciences [q-bio]/Biochemistry, Molecular Biology, 030304 developmental biology, posttranslational modification, MESH: Humans, MESH: Apoptosis, MESH : Humans, Ubiquitination, [SDV.BDD.MOR]Life Sciences [q-bio]/Development Biology/Morphogenesis, protease, MESH: Cell Line, [SDV.BDD.EO]Life Sciences [q-bio]/Development Biology/Embryology and Organogenesis, MESH : Two-Hybrid System Techniques, Mutagenesis, Site-Directed, biology.protein, Cancer research, MESH: Ubiquitination, MESH : Apoptosis
Abstract: International audience; Patched (Ptc), the main receptor for Sonic Hedgehog, is a tumor suppressor. Ptc has been shown to be a dependence receptor, and as such triggers apoptosis in the absence of its ligand. This apoptosis induction occurs through the recruitment by the Ptc intracellular domain of a caspase-activating complex, which includes the adaptor proteins DRAL and TUCAN, and the apical caspase-9. We show here that this caspase-activating complex also includes the E3 ubiquitin ligase NEDD4. We demonstrate that Ptc-mediated apoptosis and Ptc-induced caspase-9 activation require NEDD4. We show that Ptc, but not Bax, the prototypical inducer of the intrinsic cell-death pathway, triggers polyubiquitination of caspase-9. Moreover, a caspase-9 mutant that could not be ubiquitinated failed to mediate Ptc-induced apoptosis. Taken together, these data support the view that the Ptc dependence receptor specifically allows the activation of caspase-9 via its ubiquitination, which occurs via the recruitment by Ptc of NEDD4.
Published: 2012
Full Text: View/download PDF

2. Regulating TRAIL Receptor-Induced Cell Death at the Membrane: A Deadly Discussion

Author: Sarah Shirley, Olivier Micheau, Alexandre Morizot, Lipides - Nutrition - Cancer (U866) (LNC), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Bourgogne (UB)-Ecole Nationale Supérieure de Biologie Appliquée à la Nutrition et à l'Alimentation de Dijon (ENSBANA)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement, Centre Régional de Lutte contre le cancer Georges-François Leclerc [Dijon] (UNICANCER/CRLCC-CGFL), UNICANCER, This work is supported by grants of the Conseil Regional de Bourgogne, the INCa (Institut National du Cancer), Cancéropôle Grand-Est, ANR (Agence Nationale de la Recherche, ANR-06-JCJC-0103 and 07-PCV-0031), and the European Community (ApopTrain Marie Curie RTN) (O.M.). A.M., is supported by fellowships from the Ministry of Research and Education and the ARC (Association pour la Recherche sur le Cancer). S.S. is supported by the INCa., ANR-06-JCJC-0103,TRAILCHIM,TRAIL et chimiothérapies anticancéreuses(2006), Lipides - Nutrition - Cancer (U866) ( LNC ), Université de Bourgogne ( UB ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Ecole Nationale Supérieure de Biologie Appliquée à la Nutrition et à l'Alimentation de Dijon ( ENSBANA ), Centre Régional de Lutte contre le cancer - Centre Georges-François Leclerc ( CRLCC - CGFL ), and ANR-06-JCJC-0103,TRAILCHIM,TRAIL et chimiothérapies anticancéreuses ( 2006 )
Subjects: MESH: Cell Death, MESH: Signal Transduction, Cancer Research, Apoptosis, TRAIL, MESH : Models, Biological, scaffold, Cell membrane, 0302 clinical medicine, Drug Discovery, MESH: Animals, Pharmacology (medical), Receptor, death effector domain, 0303 health sciences, Cell Death, General Medicine, TRAIL-R4, 3. Good health, Cell biology, medicine.anatomical_structure, Oncology, 030220 oncology & carcinogenesis, Signal transduction, MESH : Apoptosis Regulatory Proteins, Signal Transduction, Programmed cell death, c-FLIP, death domain, medicine.drug_class, MESH : Cell Membrane, Cancer therapy, Biology, Monoclonal antibody, Models, Biological, Article, 03 medical and health sciences, medicine, Animals, Humans, Chemotherapy, [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology, MESH: Receptors, TNF-Related Apoptosis-Inducing Ligand, MESH : Receptors, TNF-Related Apoptosis-Inducing Ligand, [ SDV.BBM ] Life Sciences [q-bio]/Biochemistry, Molecular Biology, 030304 developmental biology, MESH : Signal Transduction, MESH: Humans, MESH: Apoptosis Regulatory Proteins, MESH: Apoptosis, MESH : Humans, Cell Membrane, MESH: Models, Biological, DISC, Receptors, TNF-Related Apoptosis-Inducing Ligand, MESH : Cell Death, FADD, Cancer cell, MESH : Animals, Apoptosis Regulatory Proteins, MESH : Apoptosis, MESH: Cell Membrane
Abstract: Article Open access plus; International audience; The use of TRAIL/APO2L and monoclonal antibodies targeting TRAIL receptors for cancer therapy holds great promise, due to their ability to restore cancer cell sensitivity to apoptosis in association with conventional chemotherapeutic drugs in a large variety of tumors. TRAIL-induced cell death is tightly regulated right from the membrane and at the DISC (Death-Inducing Signaling Complex) level. The following patent and literature review aims to present and highlight recent findings of the deadly discussion that determines tumor cell fate upon TRAIL engagement.
Published: 2011
Full Text: View/download PDF

3. Characterization of Unique Signature Sequences in the Divergent Maternal Protein Bcl2l10

Author: Germain Gillet, Abdel Aouacheria, François Penin, Aurélie Cornut-Thibaut, Yannis Guillemin, Institut de biologie et chimie des protéines [Lyon] (IBCP), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS), Centre de Recherche en Cancérologie de Lyon (UNICANCER/CRCL), Centre Léon Bérard [Lyon]-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM), Laboratoire de Biologie Moléculaire de la Cellule (LBMC), École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Ganivet, Agnès, Institut de biologie et chimie des protéines [Lyon] ( IBCP ), Université Claude Bernard Lyon 1 ( UCBL ), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique ( CNRS ), Centre de Recherche en Cancérologie de Lyon ( CRCL ), Université de Lyon-Université de Lyon-Centre Léon Bérard [Lyon]-Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ), Laboratoire de Biologie Moléculaire de la Cellule ( LBMC ), École normale supérieure - Lyon ( ENS Lyon ) -Université Claude Bernard Lyon 1 ( UCBL ), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ), and École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL)
Subjects: MESH : Cell Line, MESH : Molecular Sequence Data, Amino Acid Motifs, MESH: Amino Acid Sequence, MESH: Base Sequence, MESH : Proto-Oncogene Proteins c-bcl-2, [ SDV.CAN ] Life Sciences [q-bio]/Cancer, MESH: INDEL Mutation, protein sequence, MESH: Amino Acid Motifs, MESH: Protein Structure, Tertiary, 0302 clinical medicine, INDEL Mutation, Databases, Genetic, genetic polymorphism, MESH : Female, MESH: Animals, MESH: Genetic Variation, [SDV.BDD]Life Sciences [q-bio]/Development Biology, Peptide sequence, MESH: Databases, Genetic, MESH: Evolution, Molecular, Sequence Deletion, Genetics, chemistry.chemical_classification, 0303 health sciences, MESH : Amino Acid Sequence, MESH : Sequence Alignment, apoptosis, Vertebrate, MESH: Sequence Deletion, Amino acid, Proto-Oncogene Proteins c-bcl-2, MESH: Calcium, 030220 oncology & carcinogenesis, Female, MESH : Protein Structure, Tertiary, MESH : Amino Acid Motifs, Molecular Sequence Data, MESH: Sequence Alignment, [SDV.CAN]Life Sciences [q-bio]/Cancer, Sequence alignment, Biology, Cell Line, MESH: Oocytes, Evolution, Molecular, 03 medical and health sciences, Bcl-2 family, MESH : Genetic Variation, biology.animal, evolution, [SDV.BDD] Life Sciences [q-bio]/Development Biology, Genetic variation, Homologous chromosome, Animals, Humans, MESH : HeLa Cells, MESH : Evolution, Molecular, Amino Acid Sequence, MESH : Calcium, MESH : Databases, Genetic, Indel, MESH : INDEL Mutation, Molecular Biology, Ecology, Evolution, Behavior and Systematics, 030304 developmental biology, MESH : Mutagenesis, Insertional, calcium, MESH: Humans, MESH: Molecular Sequence Data, Base Sequence, MESH : Sequence Deletion, MESH: Apoptosis, MESH : Humans, MESH : Oocytes, Genetic Variation, Protein Structure, Tertiary, MESH: Cell Line, Mutagenesis, Insertional, MESH: Mutagenesis, Insertional, MESH: Proto-Oncogene Proteins c-bcl-2, chemistry, MESH: HeLa Cells, Oocytes, MESH : Base Sequence, MESH : Animals, Sequence Alignment, MESH: Female, MESH : Apoptosis, HeLa Cells
Abstract: International audience; Insertions or deletions (indels) of amino acids residues have been recognized as an important source of genetic and structural divergence between paralogous Bcl-2 family members. However, these signature sequences have not so far been extensively investigated amongst orthologous Bcl-2 family proteins. Bcl2l10 is an antiapoptotic member of the Bcl-2 family that has evolved rapidly throughout the vertebrate lineage and which shows conserved abundant expression in eggs and oocytes. In this paper, we have unraveled two major sites of divergence between human Bcl2l10 and its vertebrate homologs. The first one provides length variation at the N-terminus (before the BH4 domain) and the second one is located between the predicted α5-α6 pore-forming helices, providing an unprecedented case in the superfamily of helix-bundled pore-forming proteins. These two particular indels were studied phylogenetically and through biochemical and cell biological techniques, including truncation and site-directed mutagenesis. While deletion of the N-terminal extension had no significant functional impact in HeLa cells, our results suggest that the human Bcl2l10 protein evolved a calcium-binding motif in its α5-α6 interhelical region by acquiring critical negatively charged residues. Considering the reliance of female eggs on calcium-dependent proteins and calcium-regulated processes and the exceptional longevity of oocytes in the primate lineage, we propose that this microstructural variation may be an adaptive feature associated with high maternal expression of this Bcl-2 family member.
Published: 2011
Full Text: View/download PDF

4. IRX-2, a novel immunotherapeutic, protects human T cells from tumor-induced cell death

Author: Theresa L. Whiteside, Marta Szajnik, H Brandwein, Miroslaw J. Szczepanski, J W Hadden, J Han, K Signorelli, K Quadrini, Malgorzata Czystowska, BMC, Ed., Centre de recherche Croissance et signalisation (UMR_S 845), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Centre de recherche Croissance et signalisation ( UMR_S 845 ), and Université Paris Descartes - Paris 5 ( UPD5 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS )
Subjects: Time Factors, MESH : Cytokines, T-Lymphocytes, medicine.medical_treatment, MESH : Dose-Response Relationship, Drug, Apoptosis, CD8-Positive T-Lymphocytes, Fas ligand, MESH: Dose-Response Relationship, Drug, MESH: Janus Kinase 3, Jurkat Cells, Phosphatidylinositol 3-Kinases, MESH: Jurkat Cells, STAT5 Transcription Factor, Cytotoxic T cell, MESH : Jurkat Cells, bcl-2-Associated X Protein, MESH: Cytokines, tofacitinib, Bcl-2-Like Protein 11, MESH : STAT5 Transcription Factor, MESH : CD8-Positive T-Lymphocytes, MESH: CD8-Positive T-Lymphocytes, MESH : Antineoplastic Agents, MESH : Proto-Oncogene Proteins c-akt, Cytokine, MESH : Proto-Oncogene Proteins, Cytokines, MESH: Membrane Proteins, JAK3, MESH : Apoptosis Regulatory Proteins, MESH : Time Factors, MESH : Janus Kinase 3, Programmed cell death, MESH: Cell Line, Tumor, kidney transplantation, Antineoplastic Agents, [SDV.BC]Life Sciences [q-bio]/Cellular Biology, Biology, Article, Cell Line, Tumor, Proto-Oncogene Proteins, medicine, Humans, MESH: bcl-2-Associated X Protein, [SDV.BC] Life Sciences [q-bio]/Cellular Biology, Molecular Biology, Protein kinase B, PI3K/AKT/mTOR pathway, MESH : T-Lymphocytes, MESH: Humans, Dose-Response Relationship, Drug, MESH : bcl-2-Associated X Protein, MESH : Cell Line, Tumor, [ SDV.BC ] Life Sciences [q-bio]/Cellular Biology, MESH: Proto-Oncogene Proteins c-akt, MESH: Apoptosis Regulatory Proteins, MESH: Apoptosis, MESH: STAT5 Transcription Factor, MESH : Humans, MESH: Time Factors, MESH : Phosphatidylinositol 3-Kinases, Janus Kinase 3, Membrane Proteins, Cell Biology, Molecular biology, MESH: Proto-Oncogene Proteins, MESH: T-Lymphocytes, MESH : Membrane Proteins, MESH: Phosphatidylinositol 3-Kinases, MESH: Antineoplastic Agents, Apoptosis Regulatory Proteins, Proto-Oncogene Proteins c-akt, MESH : Apoptosis, CD8
Abstract: International audience; IRX-2 is a cytokine-based biologic agent that has the potential to enhance antitumor immune responses. We investigated whether IRX-2 can protect T cells from tumor-induced apoptosis. Tumor-derived microvesicles (MV) expressing FasL were purified from supernatants of tumor cells and incubated with activated CD8(+) T cells. MV induced significant CD8(+) T-cell apoptosis, as evidenced by Annexin binding (64.4+/-6.4%), caspase activation (58.1+/-7.6%), a loss of mitochondrial membrane potential (82.9+/-3.9%) and DNA fragmentation. T-cell pretreatment with IRX-2 prevented apoptosis. IRX-2-mediated cytoprotection was dose and time dependent and was comparable to effects of IL-2, IL-7 or IL-15. IRX-2 prevented MV-induced downregulation of JAK3 and TCRzeta chain and induced STAT5 activation in T cells. IRX-2 prevented MV-induced Bax and Bim upregulation (P
Published: 2009
Full Text: View/download PDF

5. CD40 Ligand Protects from TRAIL-Induced Apoptosis in Follicular Lymphomas through NF-κB Activation and Up-Regulation of c-FLIP and Bcl-xL

Author: Patricia Amé-Thomas, Thierry Lamy, Olivier Micheau, Alexandre Morizot, Marion Travert, G. Semana, Thierry Guillaudeux, Céline Pangault, Thierry Fest, Karin Tarte, Microenvironnement et cancer ( MiCa ), Université de Rennes 1 ( UR1 ), Université de Rennes ( UNIV-RENNES ) -Université de Rennes ( UNIV-RENNES ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Service d'Hématologie, Immunologie et de Thérapie Cellulaire ( HITC ), Université de Rennes ( UNIV-RENNES ) -Université de Rennes ( UNIV-RENNES ) -Hôpital Pontchaillou-CHU Pontchaillou [Rennes], Lipides - Nutrition - Cancer (U866) ( LNC ), Université de Bourgogne ( UB ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Ecole Nationale Supérieure de Biologie Appliquée à la Nutrition et à l'Alimentation de Dijon ( ENSBANA ), Microenvironnement et cancer (MiCa), Université de Rennes (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Service d'Hématologie, Immunologie et de Thérapie Cellulaire (HITC), Université de Rennes (UR)-Hôpital Pontchaillou-CHU Pontchaillou [Rennes], Lipides - Nutrition - Cancer (U866) (LNC), Université de Bourgogne (UB)-Institut National de la Santé et de la Recherche Médicale (INSERM)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Ecole Nationale Supérieure de Biologie Appliquée à la Nutrition et à l'Alimentation de Dijon (ENSBANA), Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Hôpital Pontchaillou-CHU Pontchaillou [Rennes], and Le Corre, Morgane
Subjects: CD4-Positive T-Lymphocytes, MESH: Signal Transduction, MESH: CASP8 and FADD-Like Apoptosis Regulating Protein, Palatine Tonsil, CASP8 and FADD-Like Apoptosis Regulating Protein, MESH: NF-kappa B, Apoptosis, MESH: Caspase 8, Receptors, Tumor Necrosis Factor, [ SDV.CAN ] Life Sciences [q-bio]/Cancer, TNF-Related Apoptosis-Inducing Ligand, MESH: Recombinant Proteins, MESH : TNF-Related Apoptosis-Inducing Ligand, MESH: Lymphoma, Follicular, 0302 clinical medicine, MESH: Up-Regulation, [ SDV.IMM ] Life Sciences [q-bio]/Immunology, Immunology and Allergy, Cytotoxic T cell, MESH : Nitriles, Sulfones, MESH : Antigens, CD40, Lymphoma, Follicular, MESH : Up-Regulation, Cells, Cultured, B-Lymphocytes, Caspase 8, 0303 health sciences, MESH : Caspase 8, biology, NF-kappa B, MESH: CD4-Positive T-Lymphocytes, MESH: Sulfones, Recombinant Proteins, MESH: Nitriles, Up-Regulation, Cell biology, medicine.anatomical_structure, MESH : CD4-Positive T-Lymphocytes, MESH : NF-kappa B, 030220 oncology & carcinogenesis, MESH: Palatine Tonsil, [SDV.IMM]Life Sciences [q-bio]/Immunology, Signal transduction, MESH: TNF-Related Apoptosis-Inducing Ligand, Signal Transduction, MESH: Cells, Cultured, MESH: Cell Line, Tumor, [SDV.IMM] Life Sciences [q-bio]/Immunology, MESH : Recombinant Proteins, T cell, CD40 Ligand, Immunology, bcl-X Protein, [SDV.CAN]Life Sciences [q-bio]/Cancer, Bcl-xL, MESH: Antigens, CD40, MESH: bcl-X Protein, MESH : B-Lymphocytes, 03 medical and health sciences, [SDV.CAN] Life Sciences [q-bio]/Cancer, Cell Line, Tumor, MESH: B-Lymphocytes, Nitriles, MESH : Cells, Cultured, medicine, Humans, CD40 Antigens, MESH: Receptors, TNF-Related Apoptosis-Inducing Ligand, MESH : Receptors, TNF-Related Apoptosis-Inducing Ligand, MESH : Sulfones, MESH : Palatine Tonsil, MESH: CD40 Ligand, 030304 developmental biology, MESH : Signal Transduction, MESH: Humans, CD40, MESH : Cell Line, Tumor, MESH: Apoptosis, MESH : bcl-X Protein, MESH : Lymphoma, Follicular, MESH : Humans, Germinal center, MESH : CASP8 and FADD-Like Apoptosis Regulating Protein, MESH: Receptors, Tumor Necrosis Factor, MESH : CD40 Ligand, MESH : Receptors, Tumor Necrosis Factor, Receptors, TNF-Related Apoptosis-Inducing Ligand, biology.protein, MESH : Apoptosis
Abstract: The TNF family member TRAIL is emerging as a promising cytotoxic molecule for antitumor therapy. However, its mechanism of action and the possible modulation of its effect by the microenvironment in follicular lymphomas (FL) remain unknown. We show here that TRAIL is cytotoxic only against FL B cells and not against normal B cells, and that DR4 is the main receptor involved in the initiation of the apoptotic cascade. However, the engagement of CD40 by its ligand, mainly expressed on a specific germinal center CD4+ T cell subpopulation, counteracts TRAIL-induced apoptosis in FL B cells. CD40 induces a rapid RNA and protein up-regulation of c-FLIP and Bcl-xL. The induction of these antiapoptotic molecules as well as the inhibition of TRAIL-induced apoptosis by CD40 is partially abolished when NF-κB activity is inhibited by a selective inhibitor, BAY 117085. Thus, the antiapoptotic signaling of CD40, which interferes with TRAIL-induced apoptosis in FL B cells, involves NF-κB-mediated induction of c-FLIP and Bcl-xL which can respectively interfere with caspase 8 activation or mitochondrial-mediated apoptosis. These findings suggest that a cotreatment with TRAIL and an inhibitor of NF-κB signaling or a blocking anti-CD40 Ab could be of great interest in FL therapy.
Published: 2008
Full Text: View/download PDF

6. Death Receptor-Induced Apoptosis Signalling Regulation by Ezrin Is Cell Type Dependent and Occurs in a DISC-Independent Manner in Colon Cancer Cells

Author: Elisabetta Iessi, Luciana Zischler, Aurélie Etringer, Marion Bergeret, Aymeric Morlé, Guillaume Jacquemin, Alexandre Morizot, Sarah Shirley, Najoua Lalaoui, Selene L Elifio-Esposito, Stefano Fais, Carmen Garrido, Eric Solary, Olivier Micheau, Lipides - Nutrition - Cancer (U866) (LNC), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Bourgogne (UB)-Ecole Nationale Supérieure de Biologie Appliquée à la Nutrition et à l'Alimentation de Dijon (ENSBANA)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement, UFR des Sciences de Santé (Université de Bourgogne), Université de Bourgogne (UB), Pós-graduação em Ciências da Saúde [Paraná, Brazil], Pontifícia Universidade Católica do Paraná, Department of Therapeutic Research and Medicines Evaluation [Rome, Italy] (Antitumor Drugs Section), Istituto Superiore di Sanità [Rome, Italy], Centre Régional de Lutte contre le cancer Georges-François Leclerc [Dijon] (UNICANCER/CRLCC-CGFL), UNICANCER, Hématopoïèse normale et pathologique, Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Gustave Roussy (IGR)-Université Paris-Sud - Paris 11 (UP11), CAPES (N° BEX4938/14-3), University of Bourgogne, Conseil Régional de Bourgogne, Institut National du Cancer, POLYNOM-174, Ligue Nationale contre le Cancer, ARC (Association pour la Recherche sur le Cancer), Cancéropôle Grand-Est, ANR-11-LABX-0021,Lipstic,Lipoprotéines et santé : prévention et traitement des maladies inflammatoires non vasculaires et du(2011), European Project, Lipides - Nutrition - Cancer (U866) ( LNC ), Université de Bourgogne ( UB ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Ecole Nationale Supérieure de Biologie Appliquée à la Nutrition et à l'Alimentation de Dijon ( ENSBANA ), Université de Bourgogne ( UB ), Department of Therapeutic Research and Medicines Evaluation [Rome, Italy] ( Antitumor Drugs Section ), Centre Régional de Lutte contre le cancer - Centre Georges-François Leclerc ( CRLCC - CGFL ), Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Institut Gustave Roussy ( IGR ) -Université Paris-Sud - Paris 11 ( UP11 ), ANR : Labex,LipSTIC,ANR-11-LABX-0021-01-LipSTIC, Micheau, Olivier, Laboratoires d'excellence - Lipoprotéines et santé : prévention et traitement des maladies inflammatoires non vasculaires et du cancer - - Lipstic2011 - ANR-11-LABX-0021 - LABX - VALID, Apoptrain, Marie Curie RTN - INCOMING, Université de Bourgogne (UB)-Institut National de la Santé et de la Recherche Médicale (INSERM)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Ecole Nationale Supérieure de Biologie Appliquée à la Nutrition et à l'Alimentation de Dijon (ENSBANA), Université Paris-Sud - Paris 11 (UP11)-Institut Gustave Roussy (IGR)-Institut National de la Santé et de la Recherche Médicale (INSERM), ANR-11-LABX-0021,Lipstic,Lipoprotéines et santé : prévention et traitement des maladies inflammatoires non vasculaires et du cancer(2011), and Istituto Superiore di Sanità (ISS)
Subjects: lcsh:Medicine, Apoptosis, macromolecular substances, environment and public health, MESH: WWOX, TNF-Related Apoptosis-Inducing Ligand, MESH: TRAIL, Phosphoserine, MESH : Phosphorylation, Cell Line, Tumor, [SDV.BBM] Life Sciences [q-bio]/Biochemistry, Molecular Biology, Humans, [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology, fas Receptor, Phosphorylation, lcsh:Science, MESH: Ezrin, [ SDV.BBM ] Life Sciences [q-bio]/Biochemistry, Molecular Biology, MESH: Death Receptor, MESH : Death Receptor, MESH: Phosphorylation, Tumor Suppressor Proteins, MESH : WWOX, MESH: Apoptosis, lcsh:R, Receptors, Death Domain, MESH: Signaling, Mitochondria, MESH : Signaling, Cytoskeletal Proteins, MESH : Ezrin, MESH : TRAIL, WW Domain-Containing Oxidoreductase, MESH : PKA, Colonic Neoplasms, MESH: PKA, lcsh:Q, Oxidoreductases, MESH : Apoptosis, Signal Transduction, Research Article
Abstract: International audience; Ezrin belongs to the ERM (ezrin-radixin-moesin) protein family and has been demonstrated to regulate early steps of Fas receptor signalling in lymphoid cells, but its contribution to TRAIL-induced cell death regulation in adherent cancer cells remains unknown. In this study we report that regulation of FasL and TRAIL-induced cell death by ezrin is cell type depen-dant. Ezrin is a positive regulator of apoptosis in T-lymphoma cell line Jurkat, but a negative regulator in colon cancer cells. Using ezrin phosphorylation or actin-binding mutants, we provide evidence that negative regulation of death receptor-induced apoptosis by ezrin occurs in a cytoskeleton-and DISC-independent manner, in colon cancer cells. Remarkably, inhibition of apoptosis induced by these ligands was found to be tightly associated with regulation of ezrin phosphorylation on serine 66, the tumor suppressor gene WWOX and activation of PKA. Deficiency in WWOX expression in the liver cancer SK-HEP1 or the pancreatic Mia PaCa-2 cell lines as well as WWOX silencing or modulation of PKA activation by pharmacological regulators, in the colon cancer cell line SW480, abrogated regulation of TRAIL signalling by ezrin. Altogether our results show that death receptor pro-apoptotic signalling regulation by ezrin can occur downstream of the DISC in colon cancer cells.
Published: 2015
Full Text: View/download PDF

7. Cooperation of amphiregulin and insulin-like growth factor-1 inhibits Bax- and Bad-mediated apoptosis via a protein kinase C-dependent pathway in non-small cell lung cancer cells.: Bad and Bax inactivation by AR/IGF1-PKC-dependent pathway

Author: Christian Brambilla, Patrick Auberger, Marie-Christine Favrot, Jean-Luc Coll, Amandine Hurbin, Laurence Dubrez-Daloz, Bernard Mari, Groupe de Recherche Sur Le Cancer du Poumon : Bases Moléculaires de la Progression Tumorale, Dépistage et Thérapie Génique, Institut Albert Bonniot-Institut National de la Santé et de la Recherche Médicale ( INSERM ), Mort cellulaire et cancer, Université de Bourgogne ( UB ) -IFR100 - Structure fédérative de recherche Santé-STIC-Institut National de la Santé et de la Recherche Médicale ( INSERM ), Physiopathologie de la survie et de la mort cellulaire et infection virale, Institut National de la Santé et de la Recherche Médicale ( INSERM ) -IFR50-Université Nice Sophia Antipolis ( UNS ), Université Côte d'Azur ( UCA ) -Université Côte d'Azur ( UCA ), Institut Albert Bonniot-Institut National de la Santé et de la Recherche Médicale (INSERM), Université de Bourgogne (UB)-IFR100 - Structure fédérative de recherche Santé-STIC-Institut National de la Santé et de la Recherche Médicale (INSERM), Université Nice Sophia Antipolis (... - 2019) (UNS), and COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-IFR50-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Côte d'Azur (UCA)
Subjects: MAPK/ERK pathway, Lung Neoplasms, Apoptosis, MESH : Insulin-Like Growth Factor I, Biochemistry, Culture Media, Serum-Free, [ SDV.CAN ] Life Sciences [q-bio]/Cancer, MESH : Flavonoids, Wortmannin, 0302 clinical medicine, MESH : 1-Phosphatidylinositol 3-Kinase, Enzyme Inhibitors, MESH : Isoenzymes, 0303 health sciences, Kinase, MESH: Culture Media, Serum-Free, 3. Good health, Cell biology, Calphostin C, 030220 oncology & carcinogenesis, Intercellular Signaling Peptides and Proteins, MESH : bcl-Associated Death Protein, MESH : Carrier Proteins, MAP Kinase Signaling System, MESH: Carrier Proteins, Naphthalenes, Article, 03 medical and health sciences, Bcl-2-associated X protein, MESH: bcl-Associated Death Protein, Humans, MESH : Lung Neoplasms, Molecular Biology, Glycoproteins, MESH: Humans, MESH : Carcinoma, Non-Small-Cell Lung, MESH: MAP Kinase Signaling System, MESH : bcl-2-Associated X Protein, MESH : Humans, Staurosporine, MESH : Glycoproteins, MESH: Lung Neoplasms, Androstadienes, MESH: Proto-Oncogene Proteins c-bcl-2, chemistry, Carrier Proteins, MESH: Flavonoids, MESH : Apoptosis, MESH: Signal Transduction, MESH : Staurosporine, MESH: Insulin-Like Growth Factor I, MESH : Models, Biological, MESH : Proto-Oncogene Proteins c-bcl-2, MESH : Culture Media, Serum-Free, chemistry.chemical_compound, Carcinoma, Non-Small-Cell Lung, Insulin-Like Growth Factor I, Protein Kinase C, Phosphoinositide-3 Kinase Inhibitors, bcl-2-Associated X Protein, MESH: Naphthalenes, Isoenzymes, Proto-Oncogene Proteins c-bcl-2, MESH: Enzyme Inhibitors, MESH: Isoenzymes, bcl-Associated Death Protein, Signal Transduction, medicine.drug, EGF Family of Proteins, MESH: Cell Line, Tumor, MESH: Glycoproteins, MESH : Androstadienes, MESH : MAP Kinase Signaling System, [SDV.CAN]Life Sciences [q-bio]/Cancer, Biology, Amphiregulin, Models, Biological, Cell Line, Tumor, MESH : Naphthalenes, medicine, MESH: bcl-2-Associated X Protein, Calphostin, MESH : Protein Kinase C, MESH: Intercellular Signaling Peptides and Proteins, MESH : Intercellular Signaling Peptides and Proteins, 030304 developmental biology, Flavonoids, MESH : Signal Transduction, MESH : Enzyme Inhibitors, MESH : Cell Line, Tumor, MESH: Apoptosis, MESH: Models, Biological, MESH: 1-Phosphatidylinositol 3-Kinase, Cell Biology, MESH: Protein Kinase C, MESH: Androstadienes, MESH: Staurosporine, biology.protein, MESH: Carcinoma, Non-Small-Cell Lung
Abstract: International audience; Amphiregulin (AR) and insulin-like growth factor-1 (IGF1) are growth factors known to promote non-small cell lung cancer (NSCLC) survival. We have previously published that 1) AR and IGF1, secreted by H358 NSCLC cells, cooperate to protect those cells and H322 NSCLC cells from serum-starved apoptosis; 2) H358 cells resist Bax-induced apoptosis through an inhibition of Bax conformational change. We show here that the antiapoptotic activity of the AR/IGF1 combination is specifically abolished by the PKC inhibitors calphostin C and staurosporine, but not by the MAPK and phosphatidylinositol 3-kinase inhibitors PD98059 and wortmannin, suggesting the involvement of a PKC-dependent and MAPK- and phosphatidylinositol 3-kinase-independent survival pathway. The PKCdelta inhibitor rottlerin restores apoptosis induced by serum deprivation. In addition, phosphorylation of PKCdelta and PKCzeta/lambda, but not of PKCalpha/beta(II), increases in serum-starved H358 cells and in H322 cells treated with an AR/IGF1 combination and is blocked by calphostin C. The combination of AR and IGF1 increases p90(rsk) and Bad phosphorylation as well as inhibiting the conformational change of Bax by a PKC-dependent mechanism. Finally, PKCdelta, PKCzeta, or p90(rsk) small interfering RNAs block the antiapoptotic activity of AR/IGF1 combination but have no effect on partial apoptosis inhibition observed with each factor used alone. Constitutively active PKC expression inhibits serum deprivation-induced apoptosis, whereas a catalytically inactive form of p90(rsk) restores it. Thus, AR and IGF1 cooperate to prevent apoptosis by activating a specific PKC-p90(rsk)-dependent pathway, which leads to Bad and Bax inactivation. This signaling pathway is different to that used by single factor.
Published: 2005
Full Text: View/download PDF

8. A role for peroxisome proliferator-activated receptor gamma in resveratrol-induced colon cancer cell apoptosis

Author: Dominique Delmas, Emeric Limagne, Alessandra Scagliarini, Virginie Aires, Annie Carlier, Bertrand Brassart, Eric Solary, Laurent Martiny, Stéphane Mandard, Michel Tarpin, Chimiothérapie et réponse immunitaire anti-tumorale (U866, Cancer, équipe 1), Lipides - Nutrition - Cancer (U866) (LNC), Université de Bourgogne (UB)-Institut National de la Santé et de la Recherche Médicale (INSERM)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Ecole Nationale Supérieure de Biologie Appliquée à la Nutrition et à l'Alimentation de Dijon (ENSBANA)-Université de Bourgogne (UB)-Institut National de la Santé et de la Recherche Médicale (INSERM)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Ecole Nationale Supérieure de Biologie Appliquée à la Nutrition et à l'Alimentation de Dijon (ENSBANA), Matrice extracellulaire et dynamique cellulaire - UMR 7369 (MEDyC), Université de Reims Champagne-Ardenne (URCA)-SFR CAP Santé (Champagne-Ardenne Picardie Santé), Université de Reims Champagne-Ardenne (URCA)-Université de Reims Champagne-Ardenne (URCA)-Centre National de la Recherche Scientifique (CNRS), Laboratoire des Sciences de l'Environnement Marin (LEMAR) (LEMAR), Institut de Recherche pour le Développement (IRD)-Institut Français de Recherche pour l'Exploitation de la Mer (IFREMER)-Université de Brest (UBO)-Institut Universitaire Européen de la Mer (IUEM), Institut de Recherche pour le Développement (IRD)-Institut national des sciences de l'Univers (INSU - CNRS)-Université de Brest (UBO)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD)-Institut national des sciences de l'Univers (INSU - CNRS)-Université de Brest (UBO)-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS), Istituto Nazionale di Fisica Nucleare, Sezione di Roma Tor Vergata (INFN, Sezione di Roma Tor Vergata), Istituto Nazionale di Fisica Nucleare (INFN), Université de Bourgogne (UB)-Institut National de la Santé et de la Recherche Médicale (INSERM)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Ecole Nationale Supérieure de Biologie Appliquée à la Nutrition et à l'Alimentation de Dijon (ENSBANA), Hématopoïèse normale et pathologique, Université Paris-Sud - Paris 11 (UP11)-Institut Gustave Roussy (IGR)-Institut National de la Santé et de la Recherche Médicale (INSERM), Laboratoire de Signalisation et Récepteurs Matriciels (SiRMa), Université de Reims Champagne-Ardenne (URCA)-Université de Reims Champagne-Ardenne (URCA)-Centre National de la Recherche Scientifique (CNRS)-Université de Reims Champagne-Ardenne (URCA)-SFR CAP Santé (Champagne-Ardenne Picardie Santé), URCA - UFR Sciences exactes et naturelles (URCA UFR SEN), Université de Reims Champagne-Ardenne (URCA), Ligue Inter-régionale Grand-Est Contre le Cancer, Conseil Régional de Bourgogne, FEDER, Lipides - Nutrition - Cancer (U866) ( LNC ), Université de Bourgogne ( UB ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Ecole Nationale Supérieure de Biologie Appliquée à la Nutrition et à l'Alimentation de Dijon ( ENSBANA ) -Université de Bourgogne ( UB ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Ecole Nationale Supérieure de Biologie Appliquée à la Nutrition et à l'Alimentation de Dijon ( ENSBANA ), Matrice extracellulaire et dynamique cellulaire - UMR 7369 ( MEDyC ), Université de Reims Champagne-Ardenne ( URCA ) -SFR CAP Santé (Champagne-Ardenne Picardie Santé), Université de Reims Champagne-Ardenne ( URCA ) -Université de Picardie Jules Verne ( UPJV ) -Université de Reims Champagne-Ardenne ( URCA ) -Université de Picardie Jules Verne ( UPJV ) -Centre National de la Recherche Scientifique ( CNRS ), Laboratoire des Sciences de l'Environnement Marin (LEMAR) ( LEMAR ), Institut de Recherche pour le Développement ( IRD ) -Institut Français de Recherche pour l'Exploitation de la Mer ( IFREMER ) -Université de Brest ( UBO ) -Institut Universitaire Européen de la Mer ( IUEM ), Institut de Recherche pour le Développement ( IRD ) -Université de Brest ( UBO ) -Centre National de la Recherche Scientifique ( CNRS ) -Institut de Recherche pour le Développement ( IRD ) -Université de Brest ( UBO ) -Centre National de la Recherche Scientifique ( CNRS ) -Centre National de la Recherche Scientifique ( CNRS ), Istituto Nazionale di Fisica Nucleare, Sezione di Roma Tor Vergata ( INFN, Sezione di Roma Tor Vergata ), National Institute for Nuclear Physics ( INFN ), Université de Bourgogne ( UB ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Ecole Nationale Supérieure de Biologie Appliquée à la Nutrition et à l'Alimentation de Dijon ( ENSBANA ), Université Paris-Sud - Paris 11 ( UP11 ) -Institut Gustave Roussy ( IGR ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Laboratoire SiRMa, Centre National de la Recherche Scientifique ( CNRS ), URCA - UFR Sciences exactes et naturelles ( URCA UFR SEN ), Université de Reims Champagne-Ardenne ( URCA ), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Bourgogne (UB)-Ecole Nationale Supérieure de Biologie Appliquée à la Nutrition et à l'Alimentation de Dijon (ENSBANA)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Bourgogne (UB)-Ecole Nationale Supérieure de Biologie Appliquée à la Nutrition et à l'Alimentation de Dijon (ENSBANA)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement, SFR CAP Santé (Champagne-Ardenne Picardie Santé), Université de Reims Champagne-Ardenne (URCA)-Université de Picardie Jules Verne (UPJV)-Université de Reims Champagne-Ardenne (URCA)-Université de Picardie Jules Verne (UPJV)-Université de Reims Champagne-Ardenne (URCA)-Centre National de la Recherche Scientifique (CNRS), Institut de Recherche pour le Développement (IRD)-Institut national des sciences de l'Univers (INSU - CNRS)-Université de Brest (UBO)-Centre National de la Recherche Scientifique (CNRS)-Institut national des sciences de l'Univers (INSU - CNRS)-Université de Brest (UBO)-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Bourgogne (UB)-Ecole Nationale Supérieure de Biologie Appliquée à la Nutrition et à l'Alimentation de Dijon (ENSBANA)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement, Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Gustave Roussy (IGR)-Université Paris-Sud - Paris 11 (UP11), Université de Reims Champagne-Ardenne (URCA)-Université de Picardie Jules Verne (UPJV)-Université de Reims Champagne-Ardenne (URCA)-Université de Picardie Jules Verne (UPJV)-Université de Reims Champagne-Ardenne (URCA)-Centre National de la Recherche Scientifique (CNRS)-SFR CAP Santé (Champagne-Ardenne Picardie Santé), Université de Reims Champagne-Ardenne (URCA)-Université de Picardie Jules Verne (UPJV)-Université de Reims Champagne-Ardenne (URCA)-Université de Picardie Jules Verne (UPJV)-Centre National de la Recherche Scientifique (CNRS), Université de Reims Champagne-Ardenne (URCA)-Université de Picardie Jules Verne (UPJV)-Université de Reims Champagne-Ardenne (URCA)-Université de Picardie Jules Verne (UPJV)-Centre National de la Recherche Scientifique (CNRS)-Université de Reims Champagne-Ardenne (URCA)-SFR CAP Santé (Champagne-Ardenne Picardie Santé), and Mandard, Stéphane
Subjects: endocrine system diseases, Colorectal cancer, Peroxisome proliferator-activated receptor, Apoptosis, Pharmacology, Resveratrol, resveratrol, MESH: Thiazolidinediones, PPAR, [ SDV.CAN ] Life Sciences [q-bio]/Cancer, chemistry.chemical_compound, 0302 clinical medicine, MESH: Stilbenes, Stilbenes, MESH : Cell Proliferation, [ SHS.INFO ] Humanities and Social Sciences/Library and information sciences, Anilides, skin and connective tissue diseases, chemistry.chemical_classification, 0303 health sciences, food and beverages, Cell cycle, 3. Good health, MESH : Thiazolidinediones, MESH : Colonic Neoplasms, colon cancer, 030220 oncology & carcinogenesis, Colonic Neoplasms, S Phase Cell Cycle Checkpoints, Rosiglitazone, hormones, hormone substitutes, and hormone antagonists, Biotechnology, medicine.drug, MESH : PPAR gamma, MESH: Cell Line, Tumor, [SHS.INFO]Humanities and Social Sciences/Library and information sciences, [SDV.CAN]Life Sciences [q-bio]/Cancer, [SDV.BC]Life Sciences [q-bio]/Cellular Biology, Biology, MESH: Anilides, [SHS.INFO] Humanities and Social Sciences/Library and information sciences, MESH : Anilides, MESH : Stilbenes, 03 medical and health sciences, [SDV.CAN] Life Sciences [q-bio]/Cancer, Cell Line, Tumor, MESH: Cell Proliferation, medicine, [SDV.BBM] Life Sciences [q-bio]/Biochemistry, Molecular Biology, Humans, [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology, [SDV.BC] Life Sciences [q-bio]/Cellular Biology, MESH : S Phase Cell Cycle Checkpoints, [ SDV.BBM ] Life Sciences [q-bio]/Biochemistry, Molecular Biology, polyphenols, 030304 developmental biology, Cell Proliferation, MESH: Colonic Neoplasms, MESH: Humans, Cell growth, MESH : Cell Line, Tumor, [ SDV.BC ] Life Sciences [q-bio]/Cellular Biology, organic chemicals, MESH: Apoptosis, MESH : Humans, medicine.disease, PPAR gamma, MESH: S Phase Cell Cycle Checkpoints, chemistry, MESH: PPAR gamma, Cancer cell, Thiazolidinediones, MESH : Apoptosis, Food Science
Abstract: Scope Resveratrol may function as a chemopreventive agent. A recent clinical study demonstrates a reduction in tumor cell proliferation in colorectal patients receiving repeated oral ingestion of resveratrol. However, gaps remain in our knowledge of the molecular mechanisms by which resveratrol exerts its chemopreventive effect. We have previously demonstrated that resveratrol induces apoptosis in colon cancer cells and that resveratrol can sensitize chemoresistant colon cancer cells to various drugs. Based on its ability to activate peroxisome proliferator-activated receptor gamma (PPARγ) in colon cancer cells, we sought to determine the implication of this nuclear transcription factor in resveratrol-induced apoptosis. Methods and results Transient transfection of cancer cells with a dominant-negative PPARγ mutant or treatment with a PPARγ antagonist (GW9662) reversed the inhibitory effect of resveratrol. Moreover, GW9662 prevented disruption of the cell cycle induced by resveratrol and consequently abrogated resveratrol-induced apoptosis. Tumor cell death was potentiated by combining resveratrol with rosiglitazone, a PPARγ agonist. Conclusion The results show that PPARγ plays a role in resveratrol-induced apoptosis of colon carcinoma cells. The combination of resveratrol with a PPARγ agonist could be a promising pharmacological approach for treatment of colorectal cancer.
Published: 2014
Full Text: View/download PDF

9. Targeting c-FLIP in cancer

Author: Olivier Micheau, Sarah Shirley, Lipides - Nutrition - Cancer (U866) (LNC), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Bourgogne (UB)-Ecole Nationale Supérieure de Biologie Appliquée à la Nutrition et à l'Alimentation de Dijon (ENSBANA)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement, Centre Régional de Lutte contre le cancer Georges-François Leclerc [Dijon] (UNICANCER/CRLCC-CGFL), UNICANCER, INCa (Polynom174), ANR-06-JCJC-0103,TRAILCHIM,TRAIL et chimiothérapies anticancéreuses(2006), European Project, Lipides - Nutrition - Cancer (U866) ( LNC ), Université de Bourgogne ( UB ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Ecole Nationale Supérieure de Biologie Appliquée à la Nutrition et à l'Alimentation de Dijon ( ENSBANA ), Centre Régional de Lutte contre le cancer - Centre Georges-François Leclerc ( CRLCC - CGFL ), ANR-06-JCJC-0103, ANR--07-PCV-0031,ANR-06-JCJC-0103, ANR--07-PCV-0031, Micheau, Olivier, Programme 'Jeunes chercheuses et jeunes chercheurs' - TRAIL et chimiothérapies anticancéreuses - - TRAILCHIM2006 - ANR-06-JCJC-0103 - JCJC - VALID, Apoptrain, Marie Curie RTN - INCOMING, and Université de Bourgogne (UB)-Institut National de la Santé et de la Recherche Médicale (INSERM)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Ecole Nationale Supérieure de Biologie Appliquée à la Nutrition et à l'Alimentation de Dijon (ENSBANA)
Subjects: Cancer Research, MESH: CASP8 and FADD-Like Apoptosis Regulating Protein, Transcription, Genetic, Regulator, CASP8 and FADD-Like Apoptosis Regulating Protein, Apoptosis, MESH : Fas Ligand Protein, MESH : RNA, Small Interfering, Ligands, MESH : TNF-Related Apoptosis-Inducing Ligand, TNF-Related Apoptosis-Inducing Ligand, 0302 clinical medicine, Neoplasms, MESH: RNA, Small Interfering, MESH: Ligands, MESH: Neoplasms, RNA, Small Interfering, Death Receptors, Cancer, Regulation of gene expression, 0303 health sciences, MESH : Ligands, MESH: Gene Expression Regulation, Neoplastic, 3. Good health, Cell biology, Gene Expression Regulation, Neoplastic, MESH : Antineoplastic Agents, Oncology, 030220 oncology & carcinogenesis, Death-inducing signaling complex, MESH: TNF-Related Apoptosis-Inducing Ligand, Programmed cell death, Fas Ligand Protein, c-FLIP, MESH : Gene Expression Regulation, Neoplastic, Antineoplastic Agents, Biology, 03 medical and health sciences, Downregulation and upregulation, [SDV.BBM] Life Sciences [q-bio]/Biochemistry, Molecular Biology, Humans, [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology, [ SDV.BBM ] Life Sciences [q-bio]/Biochemistry, Molecular Biology, 030304 developmental biology, MESH : Protein Processing, Post-Translational, MESH: Humans, MESH: Apoptosis, MESH: Transcription, Genetic, MESH : Humans, MESH : Transcription, Genetic, MESH : CASP8 and FADD-Like Apoptosis Regulating Protein, MESH : Neoplasms, MESH: Fas Ligand Protein, Flip, MESH: Protein Processing, Post-Translational, Cancer cell, MESH: Antineoplastic Agents, Protein Processing, Post-Translational, MESH : Apoptosis
Abstract: International audience; Cellular-FLICE inhibitory protein (c-FLIP) is a key anti-apoptotic regulator that inhibits cell death mediated by the death receptors Fas, DR4, DR5, and TNF-R1. Three splice variants of c-FLIP function at the DISC level by blocking the processing and activation of procaspase-8 and -10. Overexpression of c-FLIP has been identified in many different tumour types, and its downregulation in vitro has been shown to restore apoptosis mediated by CD95L and TRAIL. c-FLIP therefore represents a promising target for cancer therapy. This review focuses on the molecular mechanisms that control c-FLIP expression and current research into inhibitors of the protein. Increasing evidence supports the investigation of c-FLIP as a therapeutic target to restore an apoptotic response in cancer cells.
Published: 2013
Full Text: View/download PDF

10. L14. Immunomodulatory properties of apoptotic cells

Author: Philippe Saas, Sylvain Perruche, Interactions hôte-greffon-tumeur, ingénierie cellulaire et génique - UFC ( HOTE GREFFON ), Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Etablissement français du sang [Bourgogne-France-Comté] ( EFS [Bourgogne-France-Comté] ) -Université de Franche-Comté ( UFC ), Laboratoire d'Excellence : Lipoprotéines et Santé : prévention et Traitement des maladies Inflammatoires et du Cancer ( LabEx LipSTIC ), Institut National de la Recherche Agronomique ( INRA ) -Université Montpellier 2 - Sciences et Techniques ( UM2 ) -Université Paris-Sud - Paris 11 ( UP11 ) -École pratique des hautes études ( EPHE ) -Institut Gustave Roussy ( IGR ) -Centre Hospitalier Régional Universitaire de Nancy ( CHRU Nancy ) -Université de Bourgogne ( UB ) -Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand ( CHU Dijon ) -Centre Régional de Lutte contre le cancer - Centre Georges-François Leclerc ( CRLCC - CGFL ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Fédération Francophone de la Cancérologie Digestive, FFCD-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Etablissement français du sang [Bourgogne-France-Comté] ( EFS [Bourgogne-France-Comté] ) -Centre National de la Recherche Scientifique ( CNRS ) -Centre Hospitalier Régional Universitaire [Besançon] ( CHRU Besançon ) -Université de Franche-Comté ( UFC ), Interactions hôte-greffon-tumeur, ingénierie cellulaire et génique - UFC (UMR INSERM 1098) (HOTE GREFFON), Institut National de la Santé et de la Recherche Médicale (INSERM)-Etablissement français du sang [Bourgogne-France-Comté] (EFS [Bourgogne-France-Comté])-Université de Franche-Comté (UFC), Laboratoire d'Excellence : Lipoprotéines et Santé : prévention et Traitement des maladies Inflammatoires et du Cancer (LabEx LipSTIC), Institut National de la Recherche Agronomique (INRA)-Université Montpellier 2 - Sciences et Techniques (UM2)-Université Paris-Sud - Paris 11 (UP11)-École pratique des hautes études (EPHE)-Institut Gustave Roussy (IGR)-Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Université de Bourgogne (UB)-Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon)-Centre Régional de Lutte contre le cancer - Centre Georges-François Leclerc (CRLCC - CGFL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Fédération Francophone de la Cancérologie Digestive, FFCD-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Etablissement français du sang [Bourgogne-France-Comté] (EFS [Bourgogne-France-Comté])-Centre National de la Recherche Scientifique (CNRS)-Centre Hospitalier Régional Universitaire [Besançon] (CHRU Besançon)-Université de Franche-Comté (UFC)-Université de Montpellier (UM), Saas, Philippe, Interactions hôte-greffon-tumeur, ingénierie cellulaire et génique - UFC (UMR INSERM 1098) (RIGHT), Institut National de la Santé et de la Recherche Médicale (INSERM)-Etablissement français du sang [Bourgogne-Franche-Comté] (EFS [Bourgogne-Franche-Comté])-Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC), Institut National de la Recherche Agronomique (INRA)-Université Montpellier 2 - Sciences et Techniques (UM2)-Université Paris-Sud - Paris 11 (UP11)-École pratique des hautes études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut Gustave Roussy (IGR)-Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon)-Université de Bourgogne (UB)-Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon)-Centre Régional de Lutte contre le cancer Georges-François Leclerc [Dijon] (UNICANCER/CRLCC-CGFL), UNICANCER-UNICANCER-Institut National de la Santé et de la Recherche Médicale (INSERM)-Fédération Francophone de la Cancérologie Digestive, FFCD-Université de Montpellier (UM)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Etablissement français du sang [Bourgogne-Franche-Comté] (EFS [Bourgogne-Franche-Comté])-Centre National de la Recherche Scientifique (CNRS)-Université de Franche-Comté (UFC), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC)-Etablissement français du sang [Bourgogne-Franche-Comté] (EFS [Bourgogne-Franche-Comté]), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut Gustave Roussy (IGR)-Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Université de Bourgogne (UB)-Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon)-Centre Régional de Lutte contre le cancer Georges-François Leclerc [Dijon] (UNICANCER/CRLCC-CGFL), UNICANCER-UNICANCER-Institut National de la Santé et de la Recherche Médicale (INSERM)-Fédération Francophone de la Cancérologie Digestive, FFCD-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Etablissement français du sang [Bourgogne-Franche-Comté] (EFS [Bourgogne-Franche-Comté])-Centre National de la Recherche Scientifique (CNRS)-Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon)-Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université de Montpellier (UM), and Université de Franche-Comté (UFC)-Etablissement français du sang [Bourgogne-France-Comté] (EFS [Bourgogne-France-Comté])-Institut National de la Santé et de la Recherche Médicale (INSERM)
Subjects: MESH: Inflammation, MESH: Signal Transduction, Cell Transplantation, Neutrophils, medicine.medical_treatment, Apoptosis, MESH: T-Lymphocyte Subsets, Pharmacology, MESH: Neutrophils, T-Lymphocytes, Regulatory, MESH : Neutrophils, MESH : T-Lymphocytes, Regulatory, 0302 clinical medicine, T-Lymphocyte Subsets, [ SDV.IMM ] Life Sciences [q-bio]/Immunology, MESH: Animals, MESH : Antigen-Presenting Cells, MESH: Desensitization, Immunologic, MESH: Phagocytosis, ComputingMilieux_MISCELLANEOUS, Desensitization (medicine), MESH : Macrophages, 0303 health sciences, Phagocytes, tolerance, MESH: Dendritic Cells, MESH: Antigen-Presenting Cells, MESH : Immune Tolerance, General Medicine, MESH: Chemokines, MESH: Cell Transplantation, [SDV.IMM]Life Sciences [q-bio]/Immunology, Chemokines, Inflammation Mediators, medicine.symptom, Signal Transduction, TGF-β, MESH: Immune Tolerance, [SDV.IMM] Life Sciences [q-bio]/Immunology, MESH: Inflammation Mediators, MESH: Immunomodulation, Antigen-Presenting Cells, Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis, Inflammation, Immunomodulation, MESH : Inflammation Mediators, 03 medical and health sciences, MESH: Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis, Cell transplantation, Text mining, Phagocytosis, MESH : Phagocytosis, Immune Tolerance, medicine, Animals, Humans, MESH : Chemokines, 030304 developmental biology, MESH : Immunomodulation, MESH : Signal Transduction, MESH: Humans, MESH : Inflammation, business.industry, Macrophages, MESH: T-Lymphocytes, Regulatory, MESH: Apoptosis, MESH : Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis, MESH : Humans, MESH: Macrophages, Dendritic Cells, MESH : T-Lymphocyte Subsets, MESH : Cell Transplantation, Desensitization, Immunologic, inflammation, MESH : Dendritic Cells, MESH : Desensitization, Immunologic, MESH : Animals, business, MESH : Apoptosis, 030215 immunology
Abstract: International audience
Published: 2013
Full Text: View/download PDF

11. Intravenous infusion of donor apoptotic leukocytes before transplantation delays allogeneic islet graft rejection through regulatory T cells

Author: François Kleinclauss, Francis Bonnefoy, François Mougel, Sylvain Perruche, Bernadette Kantelip, Alfred Penfornis, Philippe Saas, Sophie Borot, Stéphanie Kury-Paulin, Service de Diabétologie - Endocrinologie [CHRU Besançon], Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon), Interactions hôte-greffon-tumeur, ingénierie cellulaire et génique - UFC (UMR INSERM 1098) (RIGHT), Institut National de la Santé et de la Recherche Médicale (INSERM)-Etablissement français du sang [Bourgogne-Franche-Comté] (EFS [Bourgogne-Franche-Comté])-Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC), Marqueurs pronostiques et facteurs de régulations des pathologies cardiaques et vasculaires - UFC ( EA 3920) (PCVP / CARDIO), Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC)-Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon), Service d'Anatomie pathologique [CHRU Besançon], Service d'urologie, andrologie et transplantation rénale, Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon)-Hôpital Saint-Jacques, Saas, Philippe, Marqueurs pronostiques et facteurs de régulations des pathologies cardiaques et vasculaires - UFC ( UR 3920) (PCVP / CARDIO), Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon)-Université de Franche-Comté (UFC), Service de diabétologie - endocrinologie, Centre Hospitalier Régional Universitaire [Besançon] ( CHRU Besançon ) -Hôpital Jean Minjoz, Interactions hôte-greffon-tumeur, ingénierie cellulaire et génique - UFC ( HOTE GREFFON ), Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Etablissement français du sang [Bourgogne-France-Comté] ( EFS [Bourgogne-France-Comté] ) -Université de Franche-Comté ( UFC ), Marqueurs pronostiques et facteurs de régulations des pathologies cardiaques et vasculaires - UFC ( PCVP / CARDIO ), Université Bourgogne Franche-Comté ( UBFC ) -Université de Franche-Comté ( UFC ) -Centre Hospitalier Régional Universitaire [Besançon] ( CHRU Besançon ), Laboratoire d'anatomie pathologique [Besancon], Centre Hospitalier Régional Universitaire [Besançon] ( CHRU Besançon ) -Hôpital Jean Minjoz-Université de Franche-Comté ( UFC ), Service d'urologie et transplantation rénale, and Centre Hospitalier Régional Universitaire [Besançon] ( CHRU Besançon )
Subjects: Graft Rejection, Endocrinology, Diabetes and Metabolism, MESH : Leukocytes, Islets of Langerhans Transplantation, Apoptosis, T-Lymphocytes, Regulatory, MESH : T-Lymphocytes, Regulatory, Mice, 0302 clinical medicine, Endocrinology, Leukocytes, MESH: Diabetes Mellitus, Experimental, [ SDV.IMM ] Life Sciences [q-bio]/Immunology, Medicine, MESH : Female, MESH: Animals, 0303 health sciences, Mice, Inbred BALB C, geography.geographical_feature_category, biology, FOXP3, General Medicine, Islet, 3. Good health, Leukocyte Transfusion, MESH : Islets of Langerhans Transplantation, 030220 oncology & carcinogenesis, [SDV.IMM]Life Sciences [q-bio]/Immunology, Female, MESH : Diabetes Mellitus, Experimental, medicine.drug, Allogeneic transplantation, [SDV.IMM] Life Sciences [q-bio]/Immunology, MESH: Mice, Inbred BALB C, MESH: Immunomodulation, MESH: Graft Rejection, MESH : Leukocyte Transfusion, Diabetes Mellitus, Experimental, Andrology, Immunomodulation, MESH: Leukocytes, 03 medical and health sciences, MESH : Mice, Internal Medicine, Animals, MESH: Mice, MESH : Mice, Inbred BALB C, 030304 developmental biology, MESH : Immunomodulation, geography, business.industry, Friend virus, MESH: Apoptosis, MESH: T-Lymphocytes, Regulatory, MESH : Graft Rejection, biology.organism_classification, Streptozotocin, medicine.disease, MESH: Leukocyte Transfusion, Transplantation, Graft-versus-host disease, MESH: Islets of Langerhans Transplantation, Immunology, MESH : Animals, business, MESH: Female, MESH : Apoptosis
Abstract: International audience; AIM: This study describes the ability of intravenous donor apoptotic leukocyte infusion before islet transplantation to delay allogeneic graft rejection and implicates regulatory T cells (T(reg)) in the effect. METHODS: Allogeneic FVB (Friend virus B-type) islet transplants were placed under the kidney capsule of BALB/c recipient mice rendered diabetic by streptozotocin. Apoptotic donor leukocytes were infused intravenously 7 days before transplantation. Foxp3/DTR/GFP transgenic C57BL/6 mice were used as recipients to show depletion of T(reg) after apoptotic cell infusion. Control mice received islet transplants without apoptotic cells. RESULTS: The graft median survival time (MST) in recipient mice was 15±1.5 days when apoptotic cells were infused 7 days prior to transplantation of a 1000-islet-containing allograft and 6±0.5 days in the control mice (P
Published: 2012
Full Text: View/download PDF

12. Wee1 inhibition potentiates Wip1-dependent p53-negative tumor cell death during chemotherapy

Author: Anastasia R. Goloudina, Elena Y. Kochetkova, Marc Bardou, Arlette Hammann, Oleg N. Demidov, Sarah Richaud, Carmen Garrido, Olga A. Fedorova, Nickolai A. Barlev, Burhan Uyanik, V Clausse, Lipides - Nutrition - Cancer (U866) ( LNC ), Université de Bourgogne ( UB ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Ecole Nationale Supérieure de Biologie Appliquée à la Nutrition et à l'Alimentation de Dijon ( ENSBANA ), Institute of Cytology of the Russian Academy of Science (St. Petersburg), Centre Régional de Lutte contre le cancer - Centre Georges-François Leclerc ( CRLCC - CGFL ), Fondation ARC, laboratoire d'excellence ARC, La Ligue Contre le Cancer CCIR-GE (14-15-00636 ), fondation scientifique russe, Lipides - Nutrition - Cancer (U866) (LNC), Université de Bourgogne (UB)-Institut National de la Santé et de la Recherche Médicale (INSERM)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Ecole Nationale Supérieure de Biologie Appliquée à la Nutrition et à l'Alimentation de Dijon (ENSBANA), Centre Régional de Lutte contre le cancer Georges-François Leclerc [Dijon] (UNICANCER/CRLCC-CGFL), and UNICANCER
Subjects: Wip1, Apoptosis, Cell Cycle Proteins, Pharmacology, MESH: G2 Phase Cell Cycle Checkpoints, Histones, MESH : Phosphorylation, Mice, MESH : Cell Cycle Proteins, MESH: Animals, MESH: Tumor Suppressor Protein p53, MESH: Histones, Kinase, Tp53 mutations, MESH : Mice, Transgenic, 3. Good health, Protein Phosphatase 2C, Survival Rate, MESH : Antineoplastic Agents, H2ax phosphorylation, P53 activation, MESH: Protein Phosphatase 2C, RNA Interference, MESH : Colorectal Neoplasms, MESH : Carrier Proteins, Histone H2ax, MESH: Mitochondria, Immunology, Human fibroblasts, MESH: Carrier Proteins, Antineoplastic Agents, MESH: Protein-Tyrosine Kinases, MESH: Protein-Serine-Threonine Kinases, MESH : Cisplatin, 03 medical and health sciences, MESH: Cell Cycle Proteins, Genotoxic stress, MESH : Protein-Tyrosine Kinases, Humans, MESH : Histones, Anticancer Therapy, MESH: DNA Damage, Cisplatin, MESH: Humans, MESH: Phosphorylation, [ SDV.BC ] Life Sciences [q-bio]/Cellular Biology, MESH : Humans, MESH : Nuclear Proteins, 030104 developmental biology, Cancer cell, MESH: Antineoplastic Agents, Carrier Proteins, MESH: Nuclear Proteins, MESH : Apoptosis, Dna-damage response, 0301 basic medicine, Cancer Research, MESH: Caspase 3, MESH : Caspase 3, Phosphorylation, Cytotoxicity, MESH : DNA Damage, Sensitization, medicine.diagnostic_test, Caspase 3, Nuclear Proteins, Protein-Tyrosine Kinases, MESH : Survival Rate, Mitochondria, G2 Phase Cell Cycle Checkpoints, Wee1, medicine.anatomical_structure, MESH : Protein Phosphatase 2C, Original Article, MESH : Mitochondria, Colorectal Neoplasms, medicine.drug, MESH : Protein-Serine-Threonine Kinases, MESH: Cell Line, Tumor, MESH: Survival Rate, MESH: Mice, Transgenic, MESH: RNA Interference, Phosphatase, Mice, Transgenic, [SDV.BC]Life Sciences [q-bio]/Cellular Biology, Biology, Protein Serine-Threonine Kinases, Flow cytometry, Cellular and Molecular Neuroscience, Cell Line, Tumor, MESH : Mice, medicine, Animals, MESH: Mice, MESH : Cell Line, Tumor, MESH: Apoptosis, Cell Biology, MESH : Tumor Suppressor Protein p53, MESH: Cisplatin, Cancer research, biology.protein, MESH : Animals, MESH : G2 Phase Cell Cycle Checkpoints, MESH : RNA Interference, Tumor Suppressor Protein p53, MESH: Colorectal Neoplasms, DNA Damage
Abstract: Inactivation of p53 found in more than half of human cancers is often associated with increased tumor resistance to anti-cancer therapy. We have previously shown that overexpression of the phosphatase Wip1 in p53-negative tumors sensitizes them to chemotherapeutic agents, while protecting normal tissues from the side effects of anti-cancer treatment. In this study, we decided to search for kinases that prevent Wip1-mediated sensitization of cancer cells, thereby interfering with efficacy of genotoxic anti-cancer drugs. To this end, we performed a flow cytometry-based screening in order to identify kinases that regulated the levels of γH2AX, which were used as readout. Another criterion of the screen was increased sensitivity of p53-negative tumor cells to cisplatin (CDDP) in a Wip1-dependent manner. We have found that a treatment with a low dose (75 nM) of MK-1775, a recently described specific chemical inhibitor of Wee1, decreases CDDP-induced H2AX phosphorylation in p53-negative cells and enhances the Wip1-sensitization of p53-negative tumors. We were able to reduce CDDP effective concentration by 40% with a combination of Wip1 overexpression and Wee1 kinase inhibition. We have observed that Wee1 inhibition potentiates Wip1-dependent tumor sensitization effect by reducing levels of Hipk2 kinase, a negative regulator of Wip1 pathway. In addition, during CDDP treatment, the combination of Wee1 inhibition and Wip1 overexpression has a mild but significant protective effect in normal cells and tissues. Our results indicate that inhibition of the negative regulators of Wip1 pathway, Wee1 and Hipk2, in p53-negative tumors could potentiate efficiency of chemotherapeutic agents without concomitant increase of cytotoxicity in normal tissues. The development and clinical use of Wee1 and Hipk1 kinase chemical inhibitors might be a promising strategy to improve anti-cancer therapy.
Published: 2016
Full Text: View/download PDF

13. CXCR3 antagonism of SDF-1(5-67) restores trabecular function and prevents retinal neurodegeneration in a rat model of ocular hypertension

Author: William Rostène, Julie Frugier, Françoise Baleux, David Godefroy, Isabelle Célérier, Serge Picaud, Françoise Brignole-Baudouin, Julie Degardin, Jeffrey K. Harrison, Christophe Baudouin, José Sahel, Alexandre Denoyer, Institut de la Vision, Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Centre de recherche des Cordeliers - Equipe 20 'ingénierie des connaissances en santé', Centre de Recherche des Cordeliers (CRC (UMR_S 872)), Université Paris Descartes - Paris 5 (UPD5)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Descartes - Paris 5 (UPD5)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Université Paris Descartes - Paris 5 (UPD5)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), University of Florida [Gainesville] (UF), Université Paris Descartes - Paris 5 (UPD5), Université Paris Descartes - Faculté de Pharmacie de Paris (UPD5 Pharmacie), Chimie des biomolécules, Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS), Centre Hospitalier National d'Ophtalmologie des Quinze-Vingts (CHNO), Centre National de la Recherche Scientifique ( CNRS ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Université Pierre et Marie Curie - Paris 6 ( UPMC ), CIC Quinze-Vingts, Assistance publique - Hôpitaux de Paris (AP-HP)-Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre Hospitalier National d'Ophtalmologie des Quinze-Vingts, Centre de Recherche des Cordeliers ( CRC (UMR_S 872) ), Université Pierre et Marie Curie - Paris 6 ( UPMC ) -Université Paris Descartes - Paris 5 ( UPD5 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ) -Université Pierre et Marie Curie - Paris 6 ( UPMC ) -Université Paris Descartes - Paris 5 ( UPD5 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ), Department of Pharmacology & Therapeutics, College of Medicine, University of Florida, Laboratory of Toxicology, Faculty of Pharmaceutical and Biological Sciences, Université Paris Descartes - Paris 5 ( UPD5 ), Chimie des Biomolécules, Institut Pasteur [Paris]-Centre National de la Recherche Scientifique ( CNRS ), This work was supported by INSERM grants for AD, DG, JD, WR and CB, by a UPMC grant for IC and JF, and by an NIH grant for JKH (AI058256)., Université Pierre et Marie Curie - Paris 6 ( UPMC ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ), Assistance publique - Hôpitaux de Paris (AP-HP) ( APHP ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre Hospitalier National d'Ophtalmologie des Quinze-Vingts, Université Pierre et Marie Curie - Paris 6 (UPMC)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Université Pierre et Marie Curie - Paris 6 (UPMC)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Faculté de Pharmacie de Paris - Université Paris Descartes (UPD5 Pharmacie), Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS), and Godefroy, David
Subjects: Retinal degeneration, Male, Visual System, Ocular hypertension, Apoptosis, MESH : Cytoprotection, MESH : Receptors, CXCR4, MESH : Receptors, CXCR3, 0302 clinical medicine, MESH: Animals, lcsh:Science, MESH: Stress, Physiological, MESH : Glaucoma, 0303 health sciences, Neurodegeneration, Anatomy, MESH : Chemokine CXCL12, Sensory Systems, 3. Good health, [SDV] Life Sciences [q-bio], MESH : Retinal Degeneration, Medicine, MESH: Chemokine CXCL12, MESH: Glaucoma, medicine.medical_specialty, MESH: Enzyme Activation, Receptors, CXCR4, Receptors, CXCR3, MESH: Retinal Degeneration, Ocular Anatomy, Caspase 3, MESH: Receptors, CXCR4, MESH: Receptors, CXCR3, 03 medical and health sciences, Humans, Rats, Long-Evans, MESH: Vision, Ocular, Biology, Intraocular Pressure, MESH: Humans, [ SDV ] Life Sciences [q-bio], lcsh:R, MESH : Humans, Glaucoma, medicine.disease, MESH : Disease Models, Animal, eye diseases, Chemokine CXCL12, MESH: Cell Line, MESH: Ocular Hypertension, Enzyme Activation, MESH: Cytoprotection, Ophthalmology, Endocrinology, chemistry, 030221 ophthalmology & optometry, Rat, lcsh:Q, Ocular Hypertension, Trabecular meshwork, MESH: Disease Models, Animal, MESH : Apoptosis, Neuroscience, MESH : Cell Line, Intraocular pressure, Anatomy and Physiology, genetic structures, [SDV]Life Sciences [q-bio], MESH : Vision, Ocular, lcsh:Medicine, chemistry.chemical_compound, MESH: Caspase 3, Molecular Cell Biology, MESH : Caspase 3, MESH : Rats, Long-Evans, MESH : Intraocular Pressure, Multidisciplinary, Cell Death, MESH : Rats, Retinal Degeneration, Animal Models, MESH : Trabecular Meshwork, medicine.anatomical_structure, Research Article, MESH: Rats, MESH : Male, Cell Line, Model Organisms, MESH: Intraocular Pressure, MESH: Rats, Long-Evans, Stress, Physiological, Trabecular Meshwork, Ocular System, Internal medicine, medicine, MESH : Ocular Hypertension, Animals, MESH : Stress, Physiological, Vision, Ocular, 030304 developmental biology, MESH: Apoptosis, [ SDV.BC.BC ] Life Sciences [q-bio]/Cellular Biology/Subcellular Processes [q-bio.SC], Retinal, MESH: Male, Rats, MESH: Trabecular Meshwork, Disease Models, Animal, Cytoprotection, MESH : Animals, sense organs, MESH : Enzyme Activation
Abstract: International audience; Glaucoma, the most common cause of irreversible blindness, is a neuropathy commonly initiated by pathological ocular hypertension due to unknown mechanisms of trabecular meshwork degeneration. Current antiglaucoma therapy does not target the causal trabecular pathology, which may explain why treatment failure is often observed. Here we show that the chemokine CXCL12, its truncated form SDF-1(5-67), and the receptors CXCR4 and CXCR3 are expressed in human glaucomatous trabecular tissue and a human trabecular cell line. SDF-1(5-67) is produced under the control of matrix metallo-proteinases, TNF-α, and TGF-β2, factors known to be involved in glaucoma. CXCL12 protects in vitro trabecular cells from apoptotic death via CXCR4 whereas SDF-1(5-67) induces apoptosis through CXCR3 and caspase activation. Ocular administration of SDF-1(5-67) in the rat increases intraocular pressure. In contrast, administration of a selective CXCR3 antagonist in a rat model of ocular hypertension decreases intraocular pressure, prevents retinal neurodegeneration, and preserves visual function. The protective effect of CXCR3 antagonism is related to restoration of the trabecular function. These data demonstrate that proteolytic cleavage of CXCL12 is involved in trabecular pathophysiology, and that local administration of a selective CXCR3 antagonist may be a beneficial therapeutic strategy for treating ocular hypertension and subsequent retinal degeneration.
Published: 2012
Full Text: View/download PDF

14. Quercetin-mediated Mcl-1 and survivin downregulation restores TRAIL-induced apoptosis in non-Hodgkin's lymphoma B cells

Author: Anne Sophie Gallouet, Najoua Lalaoui, Guillaume Jacquemin, Thierry Guillaudeux, Elisabetta Iessi, Alexandre Morizot, Olivier Micheau, Aymeric Morlé, Carmen Garrido, Virginie Granci, Lipides - Nutrition - Cancer (U866) (LNC), Université de Bourgogne (UB)-Institut National de la Santé et de la Recherche Médicale (INSERM)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Ecole Nationale Supérieure de Biologie Appliquée à la Nutrition et à l'Alimentation de Dijon (ENSBANA), Microenvironnement et cancer (MiCa), Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Centre Régional de Lutte contre le cancer Georges-François Leclerc [Dijon] (UNICANCER/CRLCC-CGFL), UNICANCER, This work was supported by grants of the Conseil Regional de Bourgogne, the INCa (Institut National du Cancer), Cancéropôle Grand-Est, ANR (Agence Nationale de la Recherche, ANR- 07-PCV-0031), and the European Community (ApopTrain Marie Curie RTN). GJ and VG were supported by fellowships from the Ligue Nationale contre le Cancer and the INCa., ANR-07-PCVI-0031,ApoMULTI-LIB,A multivalent peptide library approach to identify functional TRAIL mimetics(2007), Lipides - Nutrition - Cancer (U866) ( LNC ), Université de Bourgogne ( UB ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Ecole Nationale Supérieure de Biologie Appliquée à la Nutrition et à l'Alimentation de Dijon ( ENSBANA ), Microenvironnement et cancer ( MiCa ), Université de Rennes 1 ( UR1 ), Université de Rennes ( UNIV-RENNES ) -Université de Rennes ( UNIV-RENNES ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Centre Régional de Lutte contre le cancer - Centre Georges-François Leclerc ( CRLCC - CGFL ), ANR-07-PCVI-0031,PCVI,A multivalent peptide library approach to identify functional TRAIL mimetics ( 2007 ), Micheau, Olivier, Physique et chimie du vivant - A multivalent peptide library approach to identify functional TRAIL mimetics - - ApoMULTI-LIB2007 - ANR-07-PCVI-0031 - PCVI - VALID, and Université de Rennes (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique )
Subjects: p53, MESH: Signal Transduction, MESH: Cell Death, medicine.medical_treatment, Follicular lymphoma, TRAIL, Antioxidants, Inhibitor of Apoptosis Proteins, MESH : Proto-Oncogene Proteins c-bcl-2, quercetin, TNF-Related Apoptosis-Inducing Ligand, MESH : TNF-Related Apoptosis-Inducing Ligand, 0302 clinical medicine, MESH : Lymphoma, B-Cell, immune system diseases, hemic and lymphatic diseases, bax, MESH: Up-Regulation, MESH : Inhibitor of Apoptosis Proteins, Caspase 10, MESH: Tumor Suppressor Protein p53, MESH : Up-Regulation, 0303 health sciences, Cell Death, apoptosis, Hematology, MESH: Drug Resistance, Neoplasm, Mitochondria, Up-Regulation, 3. Good health, Cytokine, MESH : Drug Resistance, Neoplasm, Proto-Oncogene Proteins c-bcl-2, caspases, 030220 oncology & carcinogenesis, MESH : Quercetin, MESH : Antioxidants, MESH : Mitochondria, MESH: Quercetin, MESH: TNF-Related Apoptosis-Inducing Ligand, Signal Transduction, Death Domain Receptor Signaling Adaptor Proteins, Programmed cell death, Lymphoma, B-Cell, MESH: Cell Line, Tumor, MESH: Mitochondria, Biology, survivin, 03 medical and health sciences, Downregulation and upregulation, follicular lymphoma, Cell Line, Tumor, Survivin, medicine, [SDV.BBM] Life Sciences [q-bio]/Biochemistry, Molecular Biology, Humans, [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology, [ SDV.BBM ] Life Sciences [q-bio]/Biochemistry, Molecular Biology, 030304 developmental biology, MESH: Lymphoma, B-Cell, MESH : Signal Transduction, MESH: Caspase 10, diffused large B cell lymphoma, MESH: Humans, MESH : Cell Line, Tumor, MESH: Apoptosis, MESH : Humans, MESH: Antioxidants, MESH: Inhibitor of Apoptosis Proteins, Mcl-1, Original Articles, medicine.disease, Lymphoma, Non-Hodgkin's lymphoma, MESH : Tumor Suppressor Protein p53, proteasome, MESH: Proto-Oncogene Proteins c-bcl-2, Drug Resistance, Neoplasm, Apoptosis, MESH : Caspase 10, MESH : Cell Death, Cancer research, Myeloid Cell Leukemia Sequence 1 Protein, Tumor Suppressor Protein p53, MESH : Apoptosis, MESH : Death Domain Receptor Signaling Adaptor Proteins, MESH: Death Domain Receptor Signaling Adaptor Proteins
Abstract: International audience; BACKGROUND: Non-Hodgkin's B-cell lymphomas account for approximately 70% of B-cell lymphomas. While its incidence is dramatically increasing worldwide, the disease is still associated with high morbidity due to ineffectiveness of conventional therapies, creating an urgent need for novel therapeutic approaches. Unconventional compounds, including polyphenols and the cytokine TRAIL, are being extensively studied for their capacity to restore apoptosis in a large number of tumors, including lymphomas. DESIGN AND METHODS: Molecular mechanisms of TRAIL-resistance and reactivation of the apoptotic machinery by quercetin in non-Hodgkin's lymphoma cell lines were determined by Hoescht, flow cytometry, Western blot, qPCR, by use of siRNA or pharmacological inhibitors of the mitochondrial pathway and by immunoprecipitation followed by post-translational modification analysis. RESULTS: Results demonstrate that quercetin, a natural flavonoid, restores TRAIL-induced cell death in resistant transformed follicular lymphoma B-cell lines, despite high Bcl-2 expression levels due to the chromosomal translocation t(14;18). Quercetin rescues mitochondrial activation by inducing the proteasomal degradation of Mcl-1 and by inhibiting survivin expression at the mRNA level, irrespective of p53. Restoration of the TRAIL pathway requires Bax and Bak but is independent of enhanced TRAIL DISC formation. CONCLUSIONS: We demonstrate that inactivation of survivin and Mcl-1 expression by quercetin is sufficient to restore TRAIL sensitivity in resistant non-Hodgkin's lymphoma B cells. Our results suggest, therefore, that combining quercetin with TRAIL treatments may be useful in the treatment of non-Hodgkin's lymphoma.
Published: 2012
Full Text: View/download PDF

15. c-mip down-regulates NF-κB activity and promotes apoptosis in podocytes

Author: Vincent Audard, Marina Candelier, Laure-Hélène Noël, André Pawlak, Georges Guellaen, Nabila Hamdaoui, Dominique Desvaux, Shao-yu Zhang, Philippe Lang, Djillali Sahali, Qingfeng Fan, Virginie Ory, Guellaen, Georges, Institut Mondor de Recherche Biomédicale (IMRB), Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Service d'histologie, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Henri Mondor-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Institut Cochin (IC UM3 (UMR 8104 / U1016)), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Service d'anatomie pathologique [CHU Necker], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Service de néphrologie et transplantation, Institut francilien de recheche en nephrologie et transplantation, IFRNT, This work was supported in part by an Avenir Program from INSERM, a grant from the French Kidney Foundation, Association pour l'Utilisation du Rein Artificiel (AURA), Assistance Publique des Hôpitaux de Paris (AP-HP, Programme hospitalier de recherche clinique) and a grant from the Fondation pour la Recherche Médicale (FRM)., Centre National de la Recherche Scientifique (CNRS)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12) - Institut National de la Santé et de la Recherche Médicale (INSERM) - IFR10, Assistance publique - Hôpitaux de Paris (AP-HP) - Hôpital Henri Mondor - Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Institut Cochin (UM3 (UMR 8104 / U1016)), Université Paris Descartes - Paris 5 (UPD5) - Institut National de la Santé et de la Recherche Médicale (INSERM) - Centre National de la Recherche Scientifique (CNRS), Assistance publique - Hôpitaux de Paris (AP-HP) - CHU Necker - Enfants Malades [AP-HP], and Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12)-IFR10
Subjects: Male, MESH : Cell Line, Nephrotic Syndrome, MESH: NF-kappa B, Apoptosis, Idiopathic Nephrotic Syndrome, MESH: Down-Regulation, Podocyte, MESH : Down-Regulation, Mice, chemistry.chemical_compound, 0302 clinical medicine, MESH: Transcription Factor RelA, MESH: Caspase 3, MESH: Up-Regulation, MESH: Microscopy, Confocal, MESH : Caspase 3, MESH: Animals, MESH: In Situ Nick-End Labeling, MESH : Up-Regulation, 0303 health sciences, Microscopy, Confocal, Caspase 3, Podocytes, NF-kappa B, MESH : Adult, MESH : Podocytes, Pathophysiology, MESH : Mice, Transgenic, Up-Regulation, medicine.anatomical_structure, 030220 oncology & carcinogenesis, MESH : NF-kappa B, MESH : In Situ Nick-End Labeling, MESH : Carrier Proteins, Adult, MESH: Mice, Transgenic, MESH : Nephrotic Syndrome, MESH : Male, Down-Regulation, Mice, Transgenic, MESH: Carrier Proteins, Biology, Cell Line, Pathology and Forensic Medicine, 03 medical and health sciences, In vivo, MESH : Mice, MESH: Podocytes, In Situ Nick-End Labeling, medicine, [SDV.BBM] Life Sciences [q-bio]/Biochemistry, Molecular Biology, Animals, Humans, [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology, MESH : Microscopy, Confocal, MESH: Mice, Adaptor Proteins, Signal Transducing, 030304 developmental biology, MESH: Humans, MESH: Apoptosis, MESH : Transcription Factor RelA, MESH : Humans, Transcription Factor RelA, NF-κB, MESH: Adult, MESH: Male, MESH: Cell Line, Antiapoptotic protein, chemistry, Cancer research, MESH : Animals, MESH: Nephrotic Syndrome, Carrier Proteins, Spatial relationship, MESH : Apoptosis
Abstract: International audience; The mechanisms of podocyte disorders in cases of idiopathic nephrotic syndrome (INS) are complex and remain incompletely elucidated. The abnormal regulation of NF-κB may play a key role in the pathophysiology of these podocyte diseases, but at present, NF-κB has not been thoroughly investigated. In this study, we report that induction of c-mip in podocytes of patients with INS is associated with a down-regulation of RelA, a potent antiapoptotic factor that belongs to the NF-κB family. Overexpression of c-mip in differentiated podocytes promotes apoptosis by inducing caspase-3 activity and up-regulating the proapoptotic protein Bax, whereas the overall levels of the antiapoptotic protein Bcl-2 was concomitantly decreased. The associated overexpression of RelA prevented the proapoptotic effects of c-mip. In addition, the targeted induction of c-mip in podocytes in vivo inhibited the expression of the RelA protein and increased the Bax/Bcl-2 ratio. The expression of both c-mip and active caspase-3 increased in focal and segmental glomerulosclerosis biopsies, and both proteins displayed a close spatial relationship. These results suggest that alterations in NF-κB activity might result from the up-regulation of c-mip and are likely to contribute to podocyte disorders in cases of INS.
Published: 2012
Full Text: View/download PDF

16. DCC constrains tumour progression via its dependence receptor activity

Author: Loraine Jarrosson-Wuilleme, Jean-Yves Scoazec, Guillaume Chazot, Marie Castets, Laura Broutier, Yann Molin, Armelle Paquet, Patrick Mehlen, Nicolas Gadot, Laetitia Mazelin, Marie Brevet, Agnès Bernet, Puisieux, Alain, Centre de Recherche en Cancérologie de Lyon (UNICANCER/CRCL), Centre Léon Bérard [Lyon]-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Centre Léon Bérard [Lyon], Anipath, UFR Médecine Lyon-RTH Laennec, Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre de Recherche en Cancérologie de Lyon ( CRCL ), Université Claude Bernard Lyon 1 ( UCBL ), and Université de Lyon-Université de Lyon-Centre Léon Bérard [Lyon]-Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS )
Subjects: Deleted in Colorectal Cancer, MESH : Mutant Proteins, MESH : Receptors, Cell Surface, Apoptosis, Dependence receptor, law.invention, MESH : Adenocarcinoma, Mice, MESH: Mutant Proteins, 0302 clinical medicine, law, Netrin, MESH : Intestinal Neoplasms, MESH: Animals, MESH: Gene Silencing, Receptor, Cells, Cultured, Cancer, MESH: Receptors, Cell Surface, 0303 health sciences, MESH: Genes, APC, Multidisciplinary, MESH : Tumor Suppressor Proteins, Genomics, Netrin-1, DCC Receptor, 3. Good health, 030220 oncology & carcinogenesis, Caspases, MESH: HEK293 Cells, Disease Progression, MESH: Disease Progression, MESH : Mutation, MESH: Cells, Cultured, Genes, APC, MESH: Mutation, Context (language use), Receptors, Cell Surface, Biology, Adenocarcinoma, MESH : Nerve Growth Factors, 03 medical and health sciences, MESH : Mice, MESH : Cells, Cultured, MESH : Fibroblasts, MESH : Gene Silencing, Intestinal Neoplasms, Genetics, [SDV.BBM] Life Sciences [q-bio]/Biochemistry, Molecular Biology, Gene silencing, Animals, Humans, MESH: Tumor Suppressor Proteins, [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology, Gene Silencing, Nerve Growth Factors, MESH: Intestinal Neoplasms, [ SDV.BBM ] Life Sciences [q-bio]/Biochemistry, Molecular Biology, MESH: Mice, 030304 developmental biology, MESH: Humans, MESH: Caspases, MESH: Nerve Growth Factors, Tumor Suppressor Proteins, MESH: Apoptosis, MESH : Humans, fungi, MESH: Adenocarcinoma, MESH : Disease Progression, Fibroblasts, MESH : Disease Models, Animal, MESH : HEK293 Cells, Disease Models, Animal, MESH : Genes, APC, HEK293 Cells, MESH: Fibroblasts, Immunology, Mutation, Cancer research, Suppressor, Mutant Proteins, MESH : Animals, MESH : Caspases, MESH: Disease Models, Animal, MESH : Apoptosis
Abstract: International audience; The role of deleted in colorectal carcinoma (DCC) as a tumour suppressor has been a matter of debate for the past 15 years. DCC gene expression is lost or markedly reduced in the majority of advanced colorectal cancers and, by functioning as a dependence receptor, DCC has been shown to induce apoptosis unless engaged by its ligand, netrin-1 (ref. 2). However, so far no animal model has supported the view that the DCC loss-of-function is causally implicated as predisposing to aggressive cancer development. To investigate the role of DCC-induced apoptosis in the control of tumour progression, here we created a mouse model in which the pro-apoptotic activity of DCC is genetically silenced. Although the loss of DCC-induced apoptosis in this mouse model is not associated with a major disorganization of the intestines, it leads to spontaneous intestinal neoplasia at a relatively low frequency. Loss of DCC-induced apoptosis is also associated with an increase in the number and aggressiveness of intestinal tumours in a predisposing APC mutant context, resulting in the development of highly invasive adenocarcinomas. These results demonstrate that DCC functions as a tumour suppressor via its ability to trigger tumour cell apoptosis.
Published: 2012
Full Text: View/download PDF

17. Class-specific effector functions of therapeutic antibodies

Author: Pascal, Virginie, Laffleur, Brice, Cogné, Michel, Contrôle de la Réponse Immune B et des Lymphoproliférations ( CRIBL ), Université de Limoges ( UNILIM ) -Génomique, Environnement, Immunité, Santé, Thérapeutique ( GEIST FR CNRS 3503 ) -Centre National de la Recherche Scientifique ( CNRS ), Université de Limoges ( UNILIM ), Contrôle de la Réponse Immune B et des Lymphoproliférations (CRIBL), Université de Limoges (UNILIM)-Génomique, Environnement, Immunité, Santé, Thérapeutique (GEIST FR CNRS 3503)-Centre National de la Recherche Scientifique (CNRS), and Université de Limoges (UNILIM)
Subjects: MESH : Cell Line, MESH: Immunoglobulins, Cell Survival, Immunoglobulins, Apoptosis, Antibodies, MESH : Antibodies, Cell Line, MESH: Antibodies, Monoclonal, MESH : Immunoglobulins, Mice, MESH : Mice, Animals, Humans, [ SDV.IMM ] Life Sciences [q-bio]/Immunology, MESH: Animals, MESH: Mice, MESH : Cell Survival, MESH: Humans, MESH: Antibodies, MESH: Apoptosis, MESH : Humans, Antibodies, Monoclonal, MESH: Cell Line, MESH: Cell Survival, MESH : Antibodies, Monoclonal, [SDV.IMM]Life Sciences [q-bio]/Immunology, MESH : Animals, MESH : Apoptosis
Abstract: International audience; Physiology usually combines polyclonal antibodies of multiple classes in a single humoral response. Beyond their common ability to bind antigens, these various classes of human immunoglobulins carry specific functions which can each serve specific goals. In many cases, the function of a monoclonal therapeutic antibody may thus be modulated according to the class of its constant domains. Depending on the immunoglobulin class, different functional assays will be used in order to evaluate the functional activity of a monoclonal antibody.
Published: 2012
Full Text: View/download PDF

18. [Antitubulin agents]

Author: Charles, Dumontet, Equipe 14, Centre de Recherche en Cancérologie de Lyon ( CRCL ), Université Claude Bernard Lyon 1 ( UCBL ), Université de Lyon-Université de Lyon-Centre Léon Bérard [Lyon]-Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ) -Université Claude Bernard Lyon 1 ( UCBL ), Université de Lyon-Université de Lyon-Centre Léon Bérard [Lyon]-Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ) -Hôpital Edouard Herriot [CHU - HCL], Hospices Civils de Lyon ( HCL ) -Hospices Civils de Lyon ( HCL ), Centre de Recherche en Cancérologie de Lyon (UNICANCER/CRCL), Centre Léon Bérard [Lyon]-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre Léon Bérard [Lyon]-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Hôpital Edouard Herriot [CHU - HCL], and Hospices Civils de Lyon (HCL)-Hospices Civils de Lyon (HCL)
Subjects: MESH: Taxoids, Angiogenesis Inhibitors, Antineoplastic Agents, Apoptosis, [SDV.CAN]Life Sciences [q-bio]/Cancer, Microtubules, [ SDV.CAN ] Life Sciences [q-bio]/Cancer, MESH: Tubulin Modulators, MESH : Angiogenesis Inhibitors, MESH : Vinca Alkaloids, Humans, MESH : ATP-Binding Cassette Transporters, MESH : Taxoids, Vinca Alkaloids, MESH : Microtubules, MESH: Angiogenesis Inhibitors, MESH: Humans, MESH: Microtubules, MESH: Apoptosis, MESH : Humans, MESH : Tubulin Modulators, Tubulin Modulators, MESH: Drug Resistance, Neoplasm, MESH : Antineoplastic Agents, MESH : Drug Resistance, Neoplasm, Drug Resistance, Neoplasm, MESH: ATP-Binding Cassette Transporters, MESH: Antineoplastic Agents, ATP-Binding Cassette Transporters, Taxoids, MESH: Vinca Alkaloids, MESH : Apoptosis
Abstract: International audience; Microtubules are dynamic filamentous cytoskeletal proteins that are an important therapeutic target in patients with tumors. Microtubule binding agents have been part of the pharmacopoeia of cancer for decades, and until the advent of targeted therapy microtubules represented the only alternative to DNA as a therapeutic target in cancer. There are currently a variety of available vinca alkaloids and taxanes and other agents, such as ixabepilone and eribulin, have also been approved. Maytansinoids have been used for the production of immunoconjugates, monoclonal antibodies covalently bound to antimitotic molecules. The screening of a variety of botanical species and marine organisms continues to yield promising new antitubulin agents with novel properties. Enhanced tumor specificity, reduced neurotoxicity, and insensitivity to chemoresistance mechanisms are the three main objectives in the current search for novel microtubule binding agents.
Published: 2011
Full Text: View/download PDF

19. Fine-Tuning Roles of Endogenous Brain-Derived Neurotrophic Factor, TrkB and Sortilin in Colorectal Cancer Cell Survival

Author: Hussein Akil, Marie-Odile Jauberteau, Carole Mélin, Muriel Mathonnet, Aurélie Perraud, Homéostasie Cellulaire et Pathologies (HCP), Université de Limoges (UNILIM)-CHU Limoges-Génomique, Environnement, Immunité, Santé, Thérapeutique (GEIST FR CNRS 3503), Service de Chirurgie digestive, endocrinienne et générale [CHU Limoges], CHU Limoges, Homéostasie Cellulaire et Pathologies ( HCP ), Université de Limoges ( UNILIM ) -CHU Limoges-Génomique, Environnement, Immunité, Santé, Thérapeutique ( GEIST FR CNRS 3503 ), and Service d'Immunologie et immunogénétique [CHU Limoges]
Subjects: [SDV]Life Sciences [q-bio], Fluorescent Antibody Technique, Apoptosis, Tropomyosin receptor kinase B, MESH : Blotting, Western, Tropomyosin receptor kinase A, MESH: Brain-Derived Neurotrophic Factor, Tropomyosin receptor kinase C, Indole Alkaloids, MESH : Receptor, trkB, 0302 clinical medicine, MESH : Receptor, trkC, Neurotrophic factors, MESH: Reverse Transcriptase Polymerase Chain Reaction, Molecular Cell Biology, Gastrointestinal Cancers, Basic Cancer Research, MESH : Cell Proliferation, Low-affinity nerve growth factor receptor, MESH: Fluorescent Antibody Technique, ComputingMilieux_MISCELLANEOUS, Cellular Stress Responses, 2. Zero hunger, 0303 health sciences, Multidisciplinary, Cell Death, biology, Reverse Transcriptase Polymerase Chain Reaction, MESH: Receptor, trkC, MESH: Receptor, trkB, MESH : Reverse Transcriptase Polymerase Chain Reaction, MESH: Enzyme-Linked Immunosorbent Assay, MESH : Enzyme-Linked Immunosorbent Assay, 3. Good health, MESH : Adaptor Proteins, Vesicular Transport, Oncology, 030220 oncology & carcinogenesis, Medicine, MESH : Colorectal Neoplasms, Cellular Types, Colorectal Neoplasms, Research Article, Neurotrophin, MESH: Cell Line, Tumor, Science, MESH : Cell Membrane, Blotting, Western, Carbazoles, Enzyme-Linked Immunosorbent Assay, [SDV.CAN]Life Sciences [q-bio]/Cancer, Gastroenterology and Hepatology, Receptors, Nerve Growth Factor, [SDV.BC]Life Sciences [q-bio]/Cellular Biology, Cell Growth, 03 medical and health sciences, MESH: Receptors, Nerve Growth Factor, MESH : Carbazoles, Cell Line, Tumor, MESH: Cell Proliferation, Humans, Receptor, trkB, MESH: Blotting, Western, Receptor, trkC, Biology, Cell Proliferation, 030304 developmental biology, Brain-derived neurotrophic factor, MESH: Humans, MESH : Cell Line, Tumor, [ SDV.BC ] Life Sciences [q-bio]/Cellular Biology, Brain-Derived Neurotrophic Factor, MESH: Apoptosis, Cell Membrane, MESH : Humans, Epithelial Cells, MESH: Adaptor Proteins, Vesicular Transport, Molecular biology, Adaptor Proteins, Vesicular Transport, MESH: Indole Alkaloids, MESH : Brain-Derived Neurotrophic Factor, MESH : Fluorescent Antibody Technique, MESH : Indole Alkaloids, nervous system, Trk receptor, Cancer research, biology.protein, MESH: Carbazoles, MESH : Receptors, Nerve Growth Factor, MESH: Colorectal Neoplasms, MESH : Apoptosis, MESH: Cell Membrane
Abstract: International audience; BACKGROUND: Neurotrophin receptors were initially identified in neural cells. They were recently detected in some cancers in association with invasiveness, but the function of these tyrosine kinase receptors was not previously investigated in colorectal cancer (CRC) cells. METHODS AND FINDINGS: We report herein that human CRC cell lines synthesize the neural growth factor Brain-derived neurotrophic factor (BDNF) under stress conditions (serum starvation). In parallel, CRC cells expressed high- (TrkB) and low-affinity (p75(NTR)) receptors at the plasma membrane, whereas TrkA and TrkC, two other high affinity receptors for NGF and NT-3, respectively, were undetectable. We demonstrate that BDNF induced cell proliferation and had an anti-apoptotic effect mediated through TrkB, as assessed by K252a, a Trk pharmacologic inhibitor. It suppressed both cell proliferation and survival of CRC cells that do not express TrkA nor TrkC. In parallel to the increase of BDNF secretion, sortilin, a protein acting as a neurotrophin transporter as well as a co-receptor for p75(NTR), was increased in the cytoplasm of primary and metastatic CRC cells, which suggests that sortilin could regulate neurotrophin transport in these cells. However, pro-BDNF, also detected in CRC cells, was co-expressed with p75(NTR) at the cell membrane and co-localized with sortilin. In contrast to BDNF, exogenous pro-BDNF induced CRC apoptosis, which suggests that a counterbalance mechanism is involved in the control of CRC cell survival, through sortilin as the co-receptor for p75(NTR), the high affinity receptor for pro-neurotrophins. Likewise, we show that BDNF and TrkB transcripts (and not p75(NTR)) are overexpressed in the patients' tumors by comparison with their adjacent normal tissues, notably in advanced stages of CRC. CONCLUSION: Taken together, these results highlight that BDNF and TrkB are essential for CRC cell growth and survival in vitro and in tumors. This autocrine loop could be of major importance to define new targeted therapies.
Published: 2011
Full Text: View/download PDF

20. Regulating TRAIL receptor-induced cell death at the membrane : a deadly discussion

Author: Shirley, Sarah, Morizot, Alexandre, Micheau, Olivier, Lipides - Nutrition - Cancer (U866) ( LNC ), Université de Bourgogne ( UB ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Ecole Nationale Supérieure de Biologie Appliquée à la Nutrition et à l'Alimentation de Dijon ( ENSBANA ), Centre Régional de Lutte contre le cancer - Centre Georges-François Leclerc ( CRLCC - CGFL ), This work is supported by grants of the Conseil Regional de Bourgogne, the INCa (Institut National du Cancer), Cancéropôle Grand-Est, ANR (Agence Nationale de la Recherche, ANR-06-JCJC-0103 and 07-PCV-0031), and the European Community (ApopTrain Marie Curie RTN) (O.M.). A.M., is supported by fellowships from the Ministry of Research and Education and the ARC (Association pour la Recherche sur le Cancer). S.S. is supported by the INCa., ANR-06-JCJC-0103,TRAILCHIM,TRAIL et chimiothérapies anticancéreuses ( 2006 ), Lipides - Nutrition - Cancer (U866) (LNC), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Bourgogne (UB)-Ecole Nationale Supérieure de Biologie Appliquée à la Nutrition et à l'Alimentation de Dijon (ENSBANA)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement, Centre Régional de Lutte contre le cancer Georges-François Leclerc [Dijon] (UNICANCER/CRLCC-CGFL), UNICANCER, and ANR-06-JCJC-0103,TRAILCHIM,TRAIL et chimiothérapies anticancéreuses(2006)
Subjects: MESH: Cell Death, MESH: Signal Transduction, MESH : Signal Transduction, MESH: Humans, MESH: Apoptosis Regulatory Proteins, MESH: Apoptosis, MESH : Cell Membrane, MESH : Humans, MESH: Models, Biological, MESH : Models, Biological, MESH : Cell Death, MESH: Animals, [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology, MESH : Animals, MESH: Receptors, TNF-Related Apoptosis-Inducing Ligand, MESH : Receptors, TNF-Related Apoptosis-Inducing Ligand, MESH : Apoptosis Regulatory Proteins, [ SDV.BBM ] Life Sciences [q-bio]/Biochemistry, Molecular Biology, MESH : Apoptosis, MESH: Cell Membrane
Abstract: Article Open access plus; International audience; The use of TRAIL/APO2L and monoclonal antibodies targeting TRAIL receptors for cancer therapy holds great promise, due to their ability to restore cancer cell sensitivity to apoptosis in association with conventional chemotherapeutic drugs in a large variety of tumors. TRAIL-induced cell death is tightly regulated right from the membrane and at the DISC (Death-Inducing Signaling Complex) level. The following patent and literature review aims to present and highlight recent findings of the deadly discussion that determines tumor cell fate upon TRAIL engagement.
Published: 2011

21. The antidiabetic drug ciglitazone induces high grade bladder cancer cells apoptosis through the up-regulation of TRAIL

Author: Sylvie Fauconnet, Hugues Bittard, Isabelle Lascombe, Marie-Laure Plissonnier, Carcinogénèse épithéliale : facteurs prédictifs et pronostiques - UFC (EA 3181) (CEF2P / CARCINO), Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC)-Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon), Service d'urologie, andrologie et transplantation rénale, Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon)-Hôpital Saint-Jacques, Carcinogénèse épithéliale : facteurs prédictifs et pronostiques - UFC ( CEF2P / CARCINO ), Centre Hospitalier Régional Universitaire [Besançon] ( CHRU Besançon ) -Université Bourgogne Franche-Comté ( UBFC ) -Université de Franche-Comté ( UFC ), Service de Néphrologie et Urologie, and Centre Hospitalier Régional Universitaire [Besançon] ( CHRU Besançon ) -Hôpital Saint-Jacques
Subjects: MESH: CASP8 and FADD-Like Apoptosis Regulating Protein, Cell cycle checkpoint, MESH : Antineoplastic Combined Chemotherapy Protocols, CASP8 and FADD-Like Apoptosis Regulating Protein, Peroxisome proliferator-activated receptor, Apoptosis, MESH: Thiazolidinediones, [ SDV.CAN ] Life Sciences [q-bio]/Cancer, Inhibitor of Apoptosis Proteins, TNF-Related Apoptosis-Inducing Ligand, Mice, 0302 clinical medicine, Antineoplastic Combined Chemotherapy Protocols, MESH: Up-Regulation, MESH : Inhibitor of Apoptosis Proteins, MESH: Animals, MESH : Transcriptional Activation, lcsh:Science, MESH : Up-Regulation, Apoptotic Signaling, chemistry.chemical_classification, 0303 health sciences, Bladder Cancer and Urothelial Neoplasias of the Urinary Tract, MESH: Proteasome Endopeptidase Complex, MESH : Mitosis, 3. Good health, Cell biology, Up-Regulation, MESH: Antineoplastic Combined Chemotherapy Protocols, Oncology, 030220 oncology & carcinogenesis, Caspases, Medicine, MESH: TNF-Related Apoptosis-Inducing Ligand, MESH : Neoplasm Grading, BH3 Interacting Domain Death Agonist Protein, MESH : PPAR gamma, G2 Phase, Transcriptional Activation, MESH: Xenograft Model Antitumor Assays, MESH: Enzyme Activation, Drug Research and Development, MESH : Cell Membrane, MESH: BH3 Interacting Domain Death Agonist Protein, MESH : Xenograft Model Antitumor Assays, 03 medical and health sciences, Ciglitazone, Survivin, MESH : Proteasome Endopeptidase Complex, Humans, Biology, MESH: Humans, MESH: Caspases, MESH : Humans, lcsh:R, Cell Membrane, MESH: Inhibitor of Apoptosis Proteins, MESH : Hypoglycemic Agents, Enzyme Activation, Genitourinary Tract Tumors, chemistry, MESH: PPAR gamma, Urinary Bladder Neoplasms, Cancer cell, lcsh:Q, Thiazolidinediones, Neoplasm Grading, MESH : Apoptosis, MESH: Receptors, Death Domain, MESH: Signal Transduction, lcsh:Medicine, MESH: Neoplasm Grading, MESH : TNF-Related Apoptosis-Inducing Ligand, Molecular Cell Biology, MESH : G2 Phase, Signaling in Cellular Processes, Cyclin B1, Caspase, Apoptotic Signaling Cascade, Multidisciplinary, biology, Cell Death, MESH : Receptors, Death Domain, Receptors, Death Domain, Bladder Cancer, Signaling Cascades, MESH: Urinary Bladder Neoplasms, MESH : Thiazolidinediones, MESH : Urinary Bladder Neoplasms, Signal Transduction, Research Article, Proteasome Endopeptidase Complex, Drugs and Devices, MESH: Cell Line, Tumor, Urology, Mitosis, [SDV.CAN]Life Sciences [q-bio]/Cancer, MESH: Hypoglycemic Agents, Cell Line, Tumor, MESH : Mice, Animals, Hypoglycemic Agents, MESH : BH3 Interacting Domain Death Agonist Protein, MESH: Mice, 030304 developmental biology, MESH : Signal Transduction, MESH : Cell Line, Tumor, MESH: Apoptosis, Cancers and Neoplasms, MESH : CASP8 and FADD-Like Apoptosis Regulating Protein, MESH: Mitosis, Xenograft Model Antitumor Assays, PPAR gamma, MESH: G2 Phase, biology.protein, Cancer research, MESH: Transcriptional Activation, MESH : Animals, MESH : Caspases, MESH : Enzyme Activation, MESH: Cell Membrane
Abstract: International audience; BACKGROUND: Ciglitazone belongs to the thiazolidinediones class of antidiabetic drug family and is a high-affinity ligand for the Peroxisome Proliferator-Activated Receptor γ (PPARγ). Apart from its antidiabetic activity, this molecule shows antineoplastic effectiveness in numerous cancer cell lines. METHODOLOGY/PRINCIPAL FINDINGS: Using RT4 (derived from a well differentiated grade I papillary tumor) and T24 (derived from an undifferentiated grade III carcinoma) bladder cancer cells, we investigated the potential of ciglitazone to induce apoptotic cell death and characterized the molecular mechanisms involved. In RT4 cells, the drug induced G2/M cell cycle arrest characterized by an overexpression of p53, p21(waf1/CIP1) and p27(Kip1) in concomitance with a decrease of cyclin B1. On the contrary, in T24 cells, it triggered apoptosis via extrinsic and intrinsic pathways. Cell cycle arrest and induction of apoptosis occurred at high concentrations through PPARγ activation-independent pathways. We show that in vivo treatment of nude mice by ciglitazone inhibits high grade bladder cancer xenograft development. We identified a novel mechanism by which ciglitazone kills cancer cells. Ciglitazone up-regulated soluble and membrane-bound TRAIL and let TRAIL-resistant T24 cells to respond to TRAIL through caspase activation, death receptor signalling pathway and Bid cleavage. We provided evidence that TRAIL-induced apoptosis is partially driven by ciglitazone-mediated down-regulation of c-FLIP and survivin protein levels through a proteasome-dependent degradation mechanism. CONCLUSIONS/SIGNIFICANCE: Therefore, ciglitazone could be clinically relevant as chemopreventive or therapeutic agent for the treatment of TRAIL-refractory high grade urothelial cancers.
Published: 2011
Full Text: View/download PDF

22. S-nitrosylation of the death receptor fas promotes fas ligand-mediated apoptosis in cancer cells

Author: Cindy Godard, Patrick Legembre, Selvakumar Subramaniam, Olivier Cauvard, Ali Bettaieb, Lissbeth Leon-Bollotte, Antonio Martinez–Ruiz, Jean-François Jeannin, Stéphanie Plenchette–Colas, Catherine Paul, Lipides - Nutrition - Cancer (U866) (LNC), Université de Bourgogne (UB)-Institut National de la Santé et de la Recherche Médicale (INSERM)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Ecole Nationale Supérieure de Biologie Appliquée à la Nutrition et à l'Alimentation de Dijon (ENSBANA), Servicio de Immunologia, Hospital Universitario de la Princesa-Instituto de Investigacion Sanitaria Princesa, Signalisation et Réponses aux Agents Infectieux et Chimiques (SeRAIC), Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES), Ligue Nationale Contre le Cancer (Comités de Sâone-et-Loire, de Nevers, de Côte d'Or, et le Cancéropole Grand Est), le gouvernement espagnol (grant CSD007-00020), Association pour la Recherche Contre le Cancer (L.L-B.), Institut National du Cancer (L.L-B.), la Région de Bourgogne (S.S.), Lipides - Nutrition - Cancer (U866) ( LNC ), Université de Bourgogne ( UB ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Ecole Nationale Supérieure de Biologie Appliquée à la Nutrition et à l'Alimentation de Dijon ( ENSBANA ), Signalisation et Réponses aux Agents Infectieux et Chimiques ( SeRAIC ), Université de Rennes 1 ( UR1 ), Université de Rennes ( UNIV-RENNES ) -Université de Rennes ( UNIV-RENNES ) -IFR140, Hospital Universitario de La Princesa-Instituto de Investigacion Sanitaria del Hospital de la Princesa, Hospital Universitario de La Princesa, and Université de Rennes (UR)
Subjects: MESH: Nitroglycerin, MESH: Signal Transduction, Time Factors, MESH: Membrane Microdomains, Apoptosis, MESH : Fas Ligand Protein, Cytoplasmic part, MESH: Lipid A, Fas ligand, Mice, Nitroglycerin, 0302 clinical medicine, MESH : Protein Transport, MESH : Female, MESH: Animals, FADD, Lipid raft, 0303 health sciences, Tumor, biology, Colon Cancer, MESH : Lipid A, MESH : Biotinylation, Gastroenterology, Fas receptor, MESH: Antigens, CD95, Protein Transport, Lipid A, MESH : Colonic Neoplasms, MESH : Nitric Oxide, MESH : Nitric Oxide Donors, 030220 oncology & carcinogenesis, Colonic Neoplasms, Death-inducing signaling complex, Female, [ SDV.MHEP.HEG ] Life Sciences [q-bio]/Human health and pathology/Hépatology and Gastroenterology, MESH : Mutation, MESH : Transfection, Signal Transduction, MESH : Time Factors, MESH: Protein Transport, Fas Ligand Protein, MESH : Mammary Neoplasms, Experimental, MESH: Mutation, MESH: Cell Line, Tumor, MESH: Mammary Neoplasms, Experimental, Nitric Oxide, Transfection, Caspase 8, 03 medical and health sciences, Membrane Microdomains, Cell Line, Tumor, MESH : Mice, Animals, Humans, Biotinylation, Nitric Oxide Donors, MESH: Biotinylation, Cysteine, fas Receptor, MESH: Mice, MESH : Protein Processing, Post-Translational, 030304 developmental biology, MESH : Signal Transduction, MESH: Colonic Neoplasms, MESH : Cysteine, MESH: Humans, Hepatology, MESH : Cell Line, Tumor, MESH: Apoptosis, MESH: Transfection, MESH : Humans, MESH: Time Factors, Mammary Neoplasms, Experimental, [SDV.MHEP.HEG]Life Sciences [q-bio]/Human health and pathology/Hépatology and Gastroenterology, MESH: Cysteine, MESH: Nitric Oxide Donors, Molecular biology, Signaling, MESH: Fas Ligand Protein, MESH : Nitroglycerin, Localization, MESH: Nitric Oxide, MESH: Protein Processing, Post-Translational, Mutation, biology.protein, MESH : Membrane Microdomains, MESH : Animals, MESH : Antigens, CD95, Protein Processing, Post-Translational, MESH: Female, MESH : Apoptosis
Abstract: International audience; BACKGROUND & AIMS: Fas belongs to the family of tumor necrosis factor receptors which induce apoptosis. Many cancer cells express Fas but do not undergo Fas-mediated apoptosis. Nitric oxide reverses this resistance by increasing levels of Fas at the plasma membrane. We studied the mechanisms by which NO affects Fas function. METHODS: Colon and mammary cancer cell lines were incubated with the NO donor glyceryl trinitrate or lipid A; S-nitrosylation of Fas was monitored using the biotin switch assay. Fas constructs that contained mutations at cysteine residues that prevent S-nitrosylation were used to investigate the involvement of S-nitrosylation in Fas-mediated cell death. Apoptosis was monitored according to morphologic criteria. RESULTS: NO induced S-nitrosylation of cysteine residues 199 and 304 in the cytoplasmic part of Fas. In cancer cells that overexpressed wild-type Fas, S-nitrosylation induced Fas recruitment to lipid rafts and sensitized the cells to Fas ligand. In cells that expressed a mutant form of Fas in which cysteine 304 was replaced by valine residue, NO-mediated translocation of Fas to lipid rafts was affected and the death-inducing signal complex and synergistic effect of glyceryl trinitrate-Fas ligand were inhibited significantly. These effects were not observed in cells that expressed Fas with a mutation at cysteine 199. CONCLUSIONS: We identified post-translational modifications (S-nitrosylation of cysteine residues 199 and 304) in the cytoplasmic domain of Fas. S-nitrosylation at cysteine 304 promotes redistribution of Fas to lipid rafts, formation of the death-inducing signal complex, and induction of cell death.
Published: 2011
Full Text: View/download PDF

23. Invariant natural killer T-cell-deficient mice display increased CCl₄ -induced hepatitis associated with CXCL1 over-expression and neutrophil infiltration

Author: Lisbonne, Mariette, L'Helgoualc'H, Annie, Nauwelaers, Gwendoline, Turlin, Bruno, Lucas, Catherine, Herbelin, André, Piquet-Pellorce, Claire, Samson, Michel, Signalisation et Réponses aux Agents Infectieux et Chimiques (SeRAIC), Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES), departement de pathologie, Laboratoire de biochimie générale, Hôpital Pontchaillou-CHU Pontchaillou [Rennes], Cytokines, hématopoïèse et réponse immune (CHRI), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-IFR140, Signalisation et Réponses aux Agents Infectieux et Chimiques ( SeRAIC ), Université de Rennes 1 ( UR1 ), Université de Rennes ( UNIV-RENNES ) -Université de Rennes ( UNIV-RENNES ) -IFR140, Université de Rennes ( UNIV-RENNES ) -Université de Rennes ( UNIV-RENNES ), Cytokines, hématopoïèse et réponse immune ( CHRI ), Université Paris Descartes - Paris 5 ( UPD5 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ), Université de Rennes (UR), and CHU Pontchaillou [Rennes]
Subjects: CXCL1/KC, Neutrophils, Chemokine CXCL1, Receptors, Antigen, T-Cell, alpha-beta, MESH : Carbon Tetrachloride, Apoptosis, MESH : Hepatocytes, Hepatitis, Animal, MESH: Neutrophils, MESH: Mice, Knockout, Hepatitis, MESH : Neutrophils, MESH: Hepatocytes, Mice, Cell Movement, MESH : Cell Movement, [ SDV.IMM ] Life Sciences [q-bio]/Immunology, MESH: Animals, MESH : Matrix Metalloproteinase 8, Carbon Tetrachloride, MESH: Cell Movement, Cells, Cultured, Mice, Knockout, Alanine, MESH: Receptors, Antigen, T-Cell, alpha-beta, MESH : Acute Disease, Neutrophil, MESH: Hepatitis, Animal, MESH : Chemokine CXCL1, Matrix Metalloproteinase 8, MESH : Receptors, Antigen, T-Cell, alpha-beta, Liver, Acute Disease, MESH: Acute Disease, [SDV.IMM]Life Sciences [q-bio]/Immunology, MESH: Cells, Cultured, MESH: Alanine, MESH : Aspartate Aminotransferases, MESH: Aspartate Aminotransferases, MESH : Mice, MESH : Cells, Cultured, Animals, MESH: Chemokine CXCL1, Aspartate Aminotransferases, MESH: Mice, MESH: Apoptosis, MESH: Carbon Tetrachloride, MESH : Liver, MESH : Natural Killer T-Cells, MESH: Natural Killer T-Cells, MESH: Matrix Metalloproteinase 8, Hepatocytes, Invariant NKT cells, MESH : Mice, Knockout, Natural Killer T-Cells, MESH : Animals, MESH : Alanine, MESH : Hepatitis, Animal, MESH : Apoptosis, MESH: Liver
Abstract: International audience; Invariant natural killer T (iNKT) cells are involved in the intrahepatic immune response and in hepatitis. In particular, iNKT lymphocytes are responsible for hepatocyte death in concanavalin A-induced hepatitis in mice. We examined the role of iNKT cells in acute hepatitis induced by a hepatotoxic agent, carbon tetrachloride (CCl(4) ). WT and iNKT cell-deficient (Jα18(-/-) ) mice were challenged with a single dose of 2.4 g/kg CCl(4) and both hepatic physiopathology and immune responses were studied. Plasma alanine and aspartate amino-transferase levels were significantly higher in Jα18(-/-) mice than in WT mice two days after CCl(4) administration. Chemokine CXCL1/keratinocyte-derived chemokine (KC) and MMP-8 were significantly higher in iNKT cell-deficient mice than in control mice. The more severe liver injury in Jα18(-/-) mice was associated with greater leukocyte infiltrate, which was enriched in neutrophils (CD11b(+) CD11c(-) Gr-1(+) cells), in agreement with CXCL1/KC and MMP-8 levels. Complementary experiments with NK-depleted animals indicate a minor role for NK cells in the liver damage found in iNKT-deficient mice. Thus, unlike for ConA-induced hepatitis, we report that iNKT cells protect the liver against acute hepatitis induced by CCl(4) and limit neutrophil infiltration.
Published: 2011
Full Text: View/download PDF

24. Overexpression of Bcl-2 in hepatocytes protects against injury but does not attenuate fibrosis in a mouse model of chronic cholestatic liver disease

Author: Bernard Fromenty, Claudia Mitchell, Alicia Mayeuf, Abdellah Mansouri, Marie-Anne Robin, Meriem Mahrouf-Yorgov, Hélène Gilgenkrantz, Institut Cochin (IC UM3 (UMR 8104 / U1016)), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Foie, métabolismes et cancer, Université de Rennes (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Centre de recherche biomédicale Bichat-Beaujon (CRB3), Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut Cochin ( UM3 (UMR 8104 / U1016) ), Université Paris Descartes - Paris 5 ( UPD5 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ), Hépatotoxicité et xénobiotiques, Université de Rennes 1 ( UR1 ), Université de Rennes ( UNIV-RENNES ) -Université de Rennes ( UNIV-RENNES ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ) -Université de Rennes 1 ( UR1 ), Université de Rennes ( UNIV-RENNES ) -Université de Rennes ( UNIV-RENNES ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Centre de recherche biomédicale Bichat-Beaujon ( CRB3 ), Université Paris Diderot - Paris 7 ( UPD7 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Université de Rennes 1 (UR1), and Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique )
Subjects: Necrosis, MESH : Blotting, Western, MESH : Hepatocytes, MESH: Lipid Peroxidation, MESH : Proto-Oncogene Proteins c-bcl-2, necrosis, MESH: Hepatocytes, Mice, 0302 clinical medicine, Fibrosis, MESH: Reverse Transcriptase Polymerase Chain Reaction, MESH : Bile Ducts, MESH: Animals, MESH: In Situ Nick-End Labeling, MESH : Ligation, Liver injury, 0303 health sciences, MESH: Electron Transport Complex I, MESH : Lipid Peroxidation, Reverse Transcriptase Polymerase Chain Reaction, Histological Techniques, MESH : Reverse Transcriptase Polymerase Chain Reaction, apoptosis, Fas receptor, MESH : Mice, Transgenic, medicine.anatomical_structure, Proto-Oncogene Proteins c-bcl-2, Caspases, Hepatocyte, MESH : In Situ Nick-End Labeling, MESH : Histological Techniques, [ SDV.MHEP.HEG ] Life Sciences [q-bio]/Human health and pathology/Hépatology and Gastroenterology, 030211 gastroenterology & hepatology, medicine.symptom, Programmed cell death, medicine.medical_specialty, MESH: Mice, Transgenic, Blotting, Western, Mice, Transgenic, Cholestasis, Intrahepatic, MESH: Histological Techniques, Biology, Pathology and Forensic Medicine, 03 medical and health sciences, Cholestasis, Internal medicine, MESH : Mice, In Situ Nick-End Labeling, medicine, Animals, MESH: Blotting, Western, Bcl-2, Ligation, Molecular Biology, MESH: Mice, 030304 developmental biology, MESH: Necrosis, Electron Transport Complex I, MESH: Caspases, MESH: Cholestasis, Intrahepatic, MESH: Apoptosis, MESH : Electron Transport Complex I, fibrosis, [SDV.MHEP.HEG]Life Sciences [q-bio]/Human health and pathology/Hépatology and Gastroenterology, Cell Biology, MESH: Ligation, medicine.disease, oxydative stress, MESH : Necrosis, Endocrinology, MESH: Proto-Oncogene Proteins c-bcl-2, Apoptosis, inflammation, Hepatocytes, MESH : Cholestasis, Intrahepatic, Bile Ducts, Lipid Peroxidation, MESH : Animals, MESH : Caspases, MESH: Bile Ducts, cholestasis, MESH : Apoptosis
Abstract: International audience; The role of hepatocyte apoptosis in the physiopathology of obstructive cholestasis is still controversial. Although some data have strongly suggested that hepatocellular cholestatic injury is due to Fas-mediated hepatocyte apoptosis, some others concluded that necrosis, rather than apoptosis, represents the main type of hepatocyte death in chronic cholestasis. Moreover, it has also been suggested that the reduced liver injury observed in the absence of Fas receptor after bile duct ligation was not due to lower hepatocyte apoptosis but to the indirect role of this receptor in non-hepatocytic cells such as cholangiocytes and inflammatory cells. The aim of this work was therefore to determine whether a protection against cell death limited to hepatocytes could be sufficient to reduce liver injury and delay cholestatic fibrosis. With this purpose, we performed bile duct ligation in transgenic mice overexpressing Bcl-2 in hepatocytes and in wild-type littermates. We found that, compared with necrosis, apoptosis was negligible in this model. Our results also showed that hepatocyte Bcl-2 expression protected hepatocytes against liver injury only in the early steps of the disease. This protection was correlated with reduced mitochondrial dysfunction and lipid peroxidation. However, in contrast to Fas receptor-deficient lpr mice, fibrosis progression was not hampered and liver inflammatory response was not reduced by Bcl-2 overexpression. These results therefore comfort the hypothesis that Fas-mediated apoptotic hepatocyte pathway is not a significant contributing factor to the clinical features observed in cholestasis. Moreover, in the absence of a blunted inflammatory response in transgenic mice, Bcl-2 protection against hepatocyte mitochondrial dysfunction and lipid peroxidation was not sufficient to block fibrosis progression.
Published: 2011
Full Text: View/download PDF

25. Dependence receptors: from basic research to drug development

Author: Patrick Mehlen, Dale E. Bredesen, Equipe 1, Centre de Recherche en Cancérologie de Lyon ( CRCL ), Centre Léon Bérard [Lyon]-Université Claude Bernard Lyon 1 ( UCBL ), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ) -Centre Léon Bérard [Lyon]-Université Claude Bernard Lyon 1 ( UCBL ), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ), Biological and Medical Informatics [San Francisco] ( BMI ), University of California [San Francisco] ( UCSF ), Centre de Recherche en Cancérologie de Lyon (UNICANCER/CRCL), Centre Léon Bérard [Lyon]-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre Léon Bérard [Lyon]-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM), Biological and Medical Informatics [San Francisco] (BMI), University of California [San Francisco] (UCSF), and University of California-University of California
Subjects: MESH : Drug Design, Angiogenesis, MESH: Low Back Pain, MESH : Prospective Studies, MESH : Aged, MESH : Receptors, Cell Surface, Apoptosis, MESH : Analysis of Variance, Dependence receptor, MESH: Pain Measurement, MESH : Models, Biological, Pharmacology, MESH: Drug Design, Ligands, medicine.disease_cause, Biochemistry, [ SDV.CAN ] Life Sciences [q-bio]/Cancer, 0302 clinical medicine, MESH : Chronic Disease, Basic research, MESH: Ligands, MESH: Double-Blind Method, MESH : Pain Measurement, MESH : Female, Receptor, MESH: Physical Therapy Modalities, MESH: Treatment Outcome, MESH: Receptors, Cell Surface, MESH: Aged, 0303 health sciences, MESH : Ligands, MESH: Middle Aged, Neurodegeneration, MESH: Disability Evaluation, MESH : Questionnaires, MESH : Adult, MESH: Patient Compliance, MESH: Interviews as Topic, Drug development, MESH : Motivation, Caspases, 030220 oncology & carcinogenesis, MESH: Cell Adhesion Molecules, Netrin Receptors, MESH : Male, MESH: Motivation, Receptors, Cell Surface, [SDV.CAN]Life Sciences [q-bio]/Cancer, MESH : Disability Evaluation, MESH : Treatment Outcome, Biology, Models, Biological, MESH : Patient Compliance, MESH : Cell Adhesion Molecules, 03 medical and health sciences, MESH: Analysis of Variance, MESH : Adolescent, medicine, Humans, MESH : Double-Blind Method, MESH : Middle Aged, Molecular Biology, 030304 developmental biology, MESH: Adolescent, MESH: Caspases, MESH: Humans, MESH: Questionnaires, MESH: Apoptosis, MESH: Chronic Disease, MESH : Humans, MESH: Models, Biological, MESH: Adult, Cell Biology, medicine.disease, MESH: Male, MESH: Prospective Studies, MESH : Low Back Pain, MESH : Physical Therapy Modalities, Drug Design, MESH : Interviews as Topic, MESH : Caspases, Carcinogenesis, Cell Adhesion Molecules, Neuroscience, MESH: Female, Function (biology), MESH : Apoptosis
Abstract: International audience; The fourth meeting on dependence receptors featured descriptions of previously unknown dependence receptors. New mechanistic data were presented on the switch between the trophic, antiapoptotic response with the proapoptotic response that occurs with loss of trophic support. The possibility that the loss of trophic support may also involve the binding of an active antitrophin was also discussed. New in vivo data were presented on the roles of dependence receptors in development, angiogenesis, oncogenesis, and neurodegeneration, as well as new therapeutic approaches based on dependence receptor function. The next meeting on dependence receptors is scheduled for 2012.
Published: 2011
Full Text: View/download PDF

26. [An alternate model of tumoral progression]

Author: Ansieau , Stéphane, Puisieux , Alain, equipe 2, Centre de Recherche en Cancérologie de Lyon ( CRCL ), Université Claude Bernard Lyon 1 ( UCBL ), Université de Lyon-Université de Lyon-Centre Léon Bérard [Lyon]-Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ) -Université Claude Bernard Lyon 1 ( UCBL ), Université de Lyon-Université de Lyon-Centre Léon Bérard [Lyon]-Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ), Institut Universitaire de France ( IUF ), Ministère de l'Éducation nationale, de l’Enseignement supérieur et de la Recherche ( M.E.N.E.S.R. ) -Ministère de l'Éducation nationale, de l’Enseignement supérieur et de la Recherche ( M.E.N.E.S.R. ) -Centre de Recherche en Cancérologie de Lyon ( CRCL ), Centre de Recherche en Cancérologie de Lyon (UNICANCER/CRCL), Centre Léon Bérard [Lyon]-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre Léon Bérard [Lyon]-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut Universitaire de France (IUF), and Ministère de l'Education nationale, de l’Enseignement supérieur et de la Recherche (M.E.N.E.S.R.)-Ministère de l'Education nationale, de l’Enseignement supérieur et de la Recherche (M.E.N.E.S.R.)-Centre de Recherche en Cancérologie de Lyon (UNICANCER/CRCL)
Subjects: MESH : Cell Aging, [SDV.CAN]Life Sciences [q-bio]/Cancer, Apoptosis, MESH : Models, Biological, Environment, Models, Biological, [ SDV.CAN ] Life Sciences [q-bio]/Cancer, Animals, Humans, MESH: Animals, Neoplasm Metastasis, MESH: Environment, Cellular Senescence, MESH: Humans, MESH: Apoptosis, Twist-Related Protein 1, MESH : Humans, MESH : Twist Transcription Factor, MESH: Models, Biological, MESH: Twist Transcription Factor, MESH : Cell Transformation, Neoplastic, MESH: Neoplasm Metastasis, MESH : Environment, Cell Transformation, Neoplastic, MESH: Cell Aging, MESH: Cell Transformation, Neoplastic, MESH : Neoplasm Metastasis, MESH : Animals, MESH : Apoptosis
Abstract: International audience; Tumor development is usually described as the result of successive waves of genetic and epigenetic changes and of Darwinian selections that allow the progressive emergence of cells with proliferation and survival advantages. According to this model of tumoral progression, the acquisition of metastatic properties is perceived as a late stage-induced response to environmentally damaging conditions in the tumor, in particular oxygen and nutriment lack. Analyzing the consequences linked to the reactivation of embryonic programmes leads, for some cancer types, to question the linearity of this model, by showing that the dissemination of cancerous or precancerous cells may begin as early as the lesions convert from a premalignant to a malignant state. We propose to review the main findings that brought about these conclusions and to discuss what consequences they might have.
Published: 2011
Full Text: View/download PDF

27. Interactions with M cells and macrophages as key steps in the pathogenesis of enterohemorrhagic Escherichia coli infections

Author: Benoit Chassaing, Nathalie Pradel, Pierre Sauvanet, Lucie Etienne-Mesmin, Jérémy Denizot, Stéphanie Blanquet-Diot, Arlette Darfeuille-Michaud, Valérie Livrelli, Laboratoire de Microbiologie et Biotechnologie des Environnements Chauds, Université de la Méditerranée - Aix-Marseille 2-Université de Provence - Aix-Marseille 1, Evolution des bactéries pathogènes et susceptibilité génétique de l'hôte (JE2526), Institut National de la Recherche Agronomique (INRA)-Université d'Auvergne - Clermont-Ferrand I (UdA), Microbiologie Environnement Digestif Santé - Clermont Auvergne (MEDIS), INRA Clermont-Ferrand-Theix-Université Clermont Auvergne (UCA), Microbiologie Environnement Digestif Santé (MEDIS), INRA Clermont-Ferrand-Theix-Université Clermont Auvergne [2017-2020] (UCA [2017-2020]), Ministere de l'Enseignement Superieur et de la Recherche [JE2526], and Institut National de Recherche Agronomique [USC-2018]
Subjects: Male, MESH: Escherichia coli O157: genetics,metabolism,physiology, Apoptosis, Pathogenesis, Shiga Toxins, Mice, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Toxins, MESH: Animals, Intestinal Mucosa, MESH : Ileum: microbiology,pathology, MESH: Microbial Viability, 0303 health sciences, MESH : Cell Survival, Microscopy, Confocal, 3. Good health, POUVOIR PATHOGENE, MESH: Cell Survival, Medical Microbiology, MESH: Microscopy, Electron, Transmission, Medicine, MESH: Bacterial Translocation, Science, LONG POLAR FIMBRIAE, PEYERS-PATCHES, CROHNS-DISEASE, SALMONELLA-TYPHIMURIUM, TISSUE TROPISM, O157-H7, EXPRESSION, STRAINS, TRANSLOCATION, COLONIZATION, MESH: Vero Cells, Microbiology, MESH : Green Fluorescent Proteins: genetics,metabolism, 03 medical and health sciences, Microscopy, Electron, Transmission, Ileum, In vivo, MESH: Ileum: microbiology,pathology, Humans, MESH : Microscopy, Confocal, Biology, Microbial Pathogens, Escherichia coli, MESH: Intestinal Mucosa: microbiology,pathology, Microbial Viability, MESH: Humans, 030306 microbiology, Macrophages, MESH: Host-Pathogen Interactions, MESH : Humans, MESH : Caco-2 Cells, MESH: Cercopithecus aethiops, [SDV.MP.BAC]Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology, In vitro, MESH: Cell Line, MESH : Escherichia coli O157: genetics,metabolism,physiology, Bacterial Translocation, BACTERIOSE, Vero cell, MESH : Bacterial Translocation, Bacterial pathogens, MESH : Cercopithecus aethiops, MESH: Shiga Toxins: metabolism, MESH : Apoptosis, MESH : Vero Cells, MESH : Cell Line, Time Factors, MESH : Models, Biological, [ SDV.MP.BAC ] Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology, medicine.disease_cause, MESH : Macrophages: microbiology,pathology,ultrastructure, Peyer's Patches, Intestinal mucosa, Gastrointestinal tract, hemic and lymphatic diseases, INFECTION, Chlorocebus aethiops, Gram Negative, MESH: Microscopy, Confocal, Enterohaemorrhagic Escherichia coli, MESH : Host-Pathogen Interactions, MESH: Peyer's Patches: microbiology,pathology, Microfold cell, Escherichia Coli, Multidisciplinary, Host-Pathogen Interaction, MESH : Microscopy, Electron, Transmission, Host-Pathogen Interactions, MESH: Caco-2 Cells, Research Article, MESH : Time Factors, Cell Survival, MESH: Macrophages: microbiology,pathology,ultrastructure, MESH : Male, Green Fluorescent Proteins, Escherichia coli O157, Escherichia coli infections, Models, Biological, Cell Line, MESH : Peyer's Patches: microbiology,pathology, MESH : Mice, medicine, Animals, MESH: Green Fluorescent Proteins: genetics,metabolism, MESH : Shiga Toxins: metabolism, Vero Cells, MESH: Mice, IMMUNITE, 030304 developmental biology, Hemolytic-uremic syndrome, MESH: Apoptosis, MESH : Intestinal Mucosa: microbiology,pathology, MESH: Time Factors, MESH: Models, Biological, MESH : Microbial Viability, DIARRHEE, MODELISATION, MESH: Male, Emerging Infectious Diseases, Cell culture, MESH : Animals, Caco-2 Cells, Ex vivo
Abstract: Enterohemorrhagic Escherichia coli (EHEC) are food-borne pathogens that can cause serious infections ranging from diarrhea to hemorrhagic colitis (HC) and hemolytic-uremic syndrome (HUS). Translocation of Shiga-toxins (Stx) from the gut lumen to underlying tissues is a decisive step in the development of the infection, but the mechanisms involved remain unclear. Many bacterial pathogens target the follicle-associated epithelium, which overlies Peyer's patches (PPs), cross the intestinal barrier through M cells and are captured by mucosal macrophages. Here, translocation across M cells, as well as survival and proliferation of EHEC strains within THP-1 macrophages were investigated using EHEC O157:H7 reference strains, isogenic mutants, and 15 EHEC strains isolated from HC/HUS patients. We showed for the first time that E. coli O157:H7 strains are able to interact in vivo with murine PPs, to translocate ex vivo through murine ileal mucosa with PPs and across an in vitro human M cell model. EHEC strains are also able to survive and to produce Stx in macrophages, which induce cell apoptosis and Stx release. In conclusion, our results suggest that the uptake of EHEC by M cells and underlying macrophages in the PP may be a critical step in Stx translocation and release in vivo. A new model for EHEC infection in humans is proposed that could help in a fuller understanding of EHEC-associated diseases.
Published: 2011
Full Text: View/download PDF

28. Chemotherapy overcomes TRAIL-R4-mediated TRAIL resistance at the DISC level

Author: Delphine Merino, Eric Solary, Guillaume Jacquemin, Philippe Saas, Najoua Lalaoui, Elisabetta Iessi, Olivier Micheau, Carmen Garrido, Bruno Chauffert, Florence Bouyer, David Lanneau, Virginie Granci, Alexandre Morizot, Mort Cellulaire et Cancer, Lipides - Nutrition - Cancer (U866) (LNC), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Bourgogne (UB)-Ecole Nationale Supérieure de Biologie Appliquée à la Nutrition et à l'Alimentation de Dijon (ENSBANA)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement, Hématopoïèse normale et pathologique, Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Gustave Roussy (IGR)-Université Paris-Sud - Paris 11 (UP11), Centre Régional de Lutte contre le cancer Georges-François Leclerc [Dijon] (UNICANCER/CRLCC-CGFL), UNICANCER, Plateforme de Biomonitoring, Etablissement français du sang [Bourgogne-Franche-Comté] (EFS [Bourgogne-Franche-Comté]), Interactions hôte-greffon-tumeur, ingénierie cellulaire et génique - UFC (UMR INSERM 1098) (RIGHT), Institut National de la Santé et de la Recherche Médicale (INSERM)-Etablissement français du sang [Bourgogne-Franche-Comté] (EFS [Bourgogne-Franche-Comté])-Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC), INCa (Polynom174), ANR-06-JCJC-0103,TRAILCHIM,TRAIL et chimiothérapies anticancéreuses(2006), European Project, Lipides - Nutrition - Cancer (U866) ( LNC ), Université de Bourgogne ( UB ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Ecole Nationale Supérieure de Biologie Appliquée à la Nutrition et à l'Alimentation de Dijon ( ENSBANA ), Université Paris-Sud - Paris 11 ( UP11 ) -Institut Gustave Roussy ( IGR ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Centre Régional de Lutte contre le cancer - Centre Georges-François Leclerc ( CRLCC - CGFL ), Etablissement français du sang [Bourgogne-France-Comté] ( EFS [Bourgogne-France-Comté] ), Interactions hôte-greffon-tumeur, ingénierie cellulaire et génique - UFC ( HOTE GREFFON ), Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Etablissement français du sang [Bourgogne-France-Comté] ( EFS [Bourgogne-France-Comté] ) -Université de Franche-Comté ( UFC ), ANR-06-JCJC-0103, ANR--07-PCV-0031,ANR-06-JCJC-0103, ANR--07-PCV-0031, Université de Bourgogne (UB)-Institut National de la Santé et de la Recherche Médicale (INSERM)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Ecole Nationale Supérieure de Biologie Appliquée à la Nutrition et à l'Alimentation de Dijon (ENSBANA), Université Paris-Sud - Paris 11 (UP11)-Institut Gustave Roussy (IGR)-Institut National de la Santé et de la Recherche Médicale (INSERM), Etablissement français du sang [Bourgogne-Franche-Comté] (EFS BFC), and Institut National de la Santé et de la Recherche Médicale (INSERM)-Etablissement français du sang [Bourgogne-Franche-Comté] (EFS BFC)-Université de Franche-Comté (UFC)
Subjects: MESH: CASP8 and FADD-Like Apoptosis Regulating Protein, MESH : Antineoplastic Combined Chemotherapy Protocols, CASP8 and FADD-Like Apoptosis Regulating Protein, TRAIL, Apoptosis, MESH : Models, Biological, Mitochondrion, MESH : RNA, Small Interfering, MESH: Caspase 8, TNF-Related Apoptosis-Inducing Ligand, MESH : TNF-Related Apoptosis-Inducing Ligand, MESH : Tumor Necrosis Factor Decoy Receptors, 0302 clinical medicine, RNA interference, Neoplasms, Antineoplastic Combined Chemotherapy Protocols, MESH: RNA, Small Interfering, MESH: Neoplasms, RNA, Small Interfering, Receptor, Sensitization, Caspase 8, 0303 health sciences, MESH : Caspase 8, MESH: Drug Resistance, Neoplasm, 3. Good health, Cell biology, MESH: Antineoplastic Combined Chemotherapy Protocols, MESH : Drug Resistance, Neoplasm, medicine.anatomical_structure, 030220 oncology & carcinogenesis, RNA Interference, MESH : GPI-Linked Proteins, MESH: TNF-Related Apoptosis-Inducing Ligand, Death Domain Receptor Signaling Adaptor Proteins, Programmed cell death, MESH: Cell Line, Tumor, c-FLIP, MESH: RNA Interference, Biology, GPI-Linked Proteins, Models, Biological, 03 medical and health sciences, Cell Line, Tumor, Receptors, Tumor Necrosis Factor, Member 10c, medicine, TRAIL-R4, Humans, cancer, Chemotherapy, [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology, MESH: Receptors, TNF-Related Apoptosis-Inducing Ligand, MESH : Receptors, TNF-Related Apoptosis-Inducing Ligand, [ SDV.BBM ] Life Sciences [q-bio]/Biochemistry, Molecular Biology, Molecular Biology, 030304 developmental biology, Original Paper, MESH: Humans, MESH : Cell Line, Tumor, MESH: Apoptosis, MESH : Humans, MESH: Models, Biological, MESH : CASP8 and FADD-Like Apoptosis Regulating Protein, Cell Biology, MESH: Tumor Necrosis Factor Decoy Receptors, MESH : Neoplasms, Receptors, TNF-Related Apoptosis-Inducing Ligand, Tumor Necrosis Factor Decoy Receptors, Drug Resistance, Neoplasm, MESH : RNA Interference, MESH: GPI-Linked Proteins, MESH : Apoptosis, MESH : Death Domain Receptor Signaling Adaptor Proteins, MESH: Death Domain Receptor Signaling Adaptor Proteins
Abstract: International audience; TNF-related apoptosis-inducing ligand or Apo2L (Apo2L/TRAIL) is a promising anti-cancer drug owing to its ability to trigger apoptosis by binding to TRAIL-R1 or TRAIL-R2, two membrane-bound receptors that are often expressed by tumor cells. TRAIL can also bind non-functional receptors such as TRAIL-R4, but controversies still exist regarding their potential to inhibit TRAIL-induced apoptosis. We show here that TRAIL-R4, expressed either endogenously or ectopically, inhibits TRAIL-induced apoptosis. Interestingly, the combination of chemotherapeutic drugs with TRAIL restores tumor cell sensitivity to apoptosis in TRAIL-R4-expressing cells. This sensitization, which mainly occurs at the death-inducing signaling complex (DISC) level, through enhanced caspase-8 recruitment and activation, is compromised by c-FLIP expression and is independent of the mitochondria. Importantly, TRAIL-R4 expression prevents TRAIL-induced tumor regression in nude mice, but tumor regression induced by TRAIL can be restored with chemotherapy. Our results clearly support a negative regulatory function for TRAIL-R4 in controlling TRAIL signaling, and unveil the ability of TRAIL-R4 to cooperate with c-FLIP to inhibit TRAIL-induced cell death.
Published: 2010
Full Text: View/download PDF

29. Dynamic processes that reflect anti-apoptotic strategies set up by HspB1 (Hsp27)

Author: Sophie Virot, Florence Manero, Stéphanie Simon, André-Patrick Arrigo, Catherine Paul, Benjamin Gibert, Lipides - Nutrition - Cancer (U866) (LNC), Université de Bourgogne (UB)-Institut National de la Santé et de la Recherche Médicale (INSERM)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Ecole Nationale Supérieure de Biologie Appliquée à la Nutrition et à l'Alimentation de Dijon (ENSBANA), Centre de génétique et de physiologie moléculaire et cellulaire (CGPhiMC), Centre National de la Recherche Scientifique (CNRS)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon, Lipides - Nutrition - Cancer (U866) ( LNC ), Université de Bourgogne ( UB ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Ecole Nationale Supérieure de Biologie Appliquée à la Nutrition et à l'Alimentation de Dijon ( ENSBANA ), Centre de génétique et de physiologie moléculaire et cellulaire ( CGPhiMC ), Université Claude Bernard Lyon 1 ( UCBL ), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique ( CNRS ), Université Claude Bernard Lyon 1 (UCBL), and Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)
Subjects: MESH: Signal Transduction, MESH : Staurosporine, MESH : Cytochromes c, MESH : HSP27 Heat-Shock Proteins, HSP27 Heat-Shock Proteins, MESH : Actins, Fluorescent Antibody Technique, Apoptosis, MESH : Blotting, Western, MESH : Antineoplastic Agents, Phytogenic, chemistry.chemical_compound, MESH : Phosphorylation, 0302 clinical medicine, MESH: Caspase 3, Staurosporine, Cytochalasin, MESH : Caspase 3, Enzyme Inhibitors, Phosphorylation, MESH: Fluorescent Antibody Technique, Heat-Shock Proteins, Cytochalasin D, Etoposide, MESH: Etoposide, 0303 health sciences, Caspase 3, Cytochromes c, MESH: Cytochromes c, MESH : Heat-Shock Response, Cell biology, Mitochondria, MESH: Antigens, CD95, MESH: Cytochalasin D, MESH: Enzyme Inhibitors, 030220 oncology & carcinogenesis, MESH : Mitochondria, Signal transduction, medicine.drug, Signal Transduction, MESH: Enzyme Activation, animal structures, MESH: Mitochondria, Blotting, Western, MESH: Antineoplastic Agents, Phytogenic, Biology, MESH : Etoposide, MESH: Actins, 03 medical and health sciences, Death-associated protein 6, Hsp27, MESH: Nucleic Acid Synthesis Inhibitors, medicine, Humans, MESH: Blotting, Western, MESH : HeLa Cells, [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology, fas Receptor, MESH: HSP27 Heat-Shock Proteins, [ SDV.BBM ] Life Sciences [q-bio]/Biochemistry, Molecular Biology, 030304 developmental biology, Nucleic Acid Synthesis Inhibitors, MESH : Signal Transduction, MESH : Enzyme Inhibitors, MESH: Humans, MESH: Phosphorylation, MESH: Apoptosis, MESH : Humans, Cell Biology, Antineoplastic Agents, Phytogenic, Actins, Enzyme Activation, MESH : Fluorescent Antibody Technique, chemistry, MESH: Heat-Shock Response, MESH: HeLa Cells, biology.protein, MESH: Staurosporine, MESH : Antigens, CD95, MESH : Cytochalasin D, MESH : Nucleic Acid Synthesis Inhibitors, MESH : Enzyme Activation, MESH : Apoptosis, Heat-Shock Response, HeLa Cells, Molecular Chaperones
Abstract: International audience; Human HspB1 (also denoted Hsp27) is an oligomeric anti-apoptotic protein that has tumorigenic and metastatic roles. To approach the structural organizations of HspB1 that are active in response to apoptosis inducers acting through different pathways, we have analyzed the relative protective efficiency induced by this protein as well its localization, oligomerization and phosphorylation. HeLa cells, that constitutively express high levels of HspB1 were treated with either etoposide, Fas agonist antibody, staurosporine or cytochalasin D. Variability in HspB1 efficiency to interfere with the different apoptotic transduction pathways induced by these agents were detected. Moreover, inducer-specific dynamic changes in HspB1 localization, native size and phosphorylation were observed, that differed from those observed after heat shock. Etoposide and Fas treatments gradually shifted HspB1 towards large but differently phosphorylated oligomeric structures. In contrast, staurosporine and cytochalasin D induced the rapid but transient formation of small oligomers before large structures were formed. These events correlated with inducer-specific phosphorylations of HspB1. Of interest, the formation of small oligomers in response to staurosporine and cytochalasin D was time correlated with the rapid disruption of F-actin. The subsequent, or gradual in the case of etoposide and Fas, formation of large oligomeric structures was a later event concomitant with the early phase of caspase activation. These observations support the hypothesis that HspB1 has the ability, through specific changes in its structural organization, to adapt and interfere at several levels with challenges triggered by different signal transduction pathways upstream of the execution phase of apoptosis.
Published: 2010
Full Text: View/download PDF

30. Bacterial Toxins and the Nervous System: Neurotoxins and Multipotential Toxins Interacting with Neuronal Cells

Author: Bernard Poulain, Michel R. Popoff, Bactéries anaérobies et Toxines, Institut Pasteur [Paris] (IP), Neurotransmission et sécrétion neuroendocrine (NSN), Centre National de la Recherche Scientifique (CNRS), Institut Pasteur [Paris], Neurotransmission et sécrétion neuroendocrine ( NSN ), and Centre National de la Recherche Scientifique ( CNRS )
Subjects: Nervous system, rho GTP-Binding Proteins, actin cytoskeleton, Health, Toxicology and Mutagenesis, [SDV]Life Sciences [q-bio], [ SDV.TOX ] Life Sciences [q-bio]/Toxicology, MESH: Neurons, MESH : Actins, Apoptosis, Review, Toxicology, Synaptic Transmission, 0302 clinical medicine, Intestinal mucosa, MESH : Glutamic Acid, Neurotoxin, MESH: Animals, Intestinal Mucosa, toxin, Neurons, 0303 health sciences, MESH : Synaptic Transmission, MESH: Exocytosis, nervous system, MESH: Glutamic Acid, 3. Good health, Cell biology, medicine.anatomical_structure, MESH: Calcium, [SDV.TOX]Life Sciences [q-bio]/Toxicology, MESH : Monomeric GTP-Binding Proteins, Enterochromaffin cell, MESH: Intestinal Mucosa, SNARE Proteins, neurotransmitter, MESH: SNARE Proteins, Cell type, Bacterial Toxins, Neurotoxins, Glutamic Acid, MESH: Monomeric GTP-Binding Proteins, Biology, Blood–brain barrier, MESH: Actins, MESH : Neurotoxins, MESH : Intestinal Mucosa, MESH : Neurons, MESH : Exocytosis, Exocytosis, small gtpases, 03 medical and health sciences, MESH : rho GTP-Binding Proteins, medicine, MESH: Synaptic Transmission, Animals, Humans, MESH : Calcium, 030304 developmental biology, Monomeric GTP-Binding Proteins, MESH: Neurotoxins, MESH: Humans, [ SDV ] Life Sciences [q-bio], MESH: Apoptosis, MESH : Humans, neurotoxin, Actin cytoskeleton, MESH : SNARE Proteins, MESH: rho GTP-Binding Proteins, Actins, MESH: Bacterial Toxins, MESH : Bacterial Toxins, Enteric nervous system, Calcium, MESH : Animals, enterotoxin, 030217 neurology & neurosurgery, MESH : Apoptosis
Abstract: International audience; Toxins are potent molecules used by various bacteria to interact with a host organism. Some of them specifically act on neuronal cells (clostridial neurotoxins) leading to characteristics neurological affections. But many other toxins are multifunctional and recognize a wider range of cell types including neuronal cells. Various enterotoxins interact with the enteric nervous system, for example by stimulating afferent neurons or inducing neurotransmitter release from enterochromaffin cells which result either in vomiting, in amplification of the diarrhea, or in intestinal inflammation process. Other toxins can pass the blood brain barrier and directly act on specific neurons.
Published: 2010
Full Text: View/download PDF

31. Stimulation of angiogenesis resulting from cooperation between macrophages and MDA-MB-231 breast cancer cells: proposed molecular mechanism and effect of tetrathiomolybdate

Author: Linda-Louise Pritchard, Ulrich Joimel, Hong Li, Rémi Varin, Emmanuel Blot, Claudine Soria, Lionel Cazin, Caroline Gest, Marc Laurent, Jeannette Soria, Jean-Pierre Vannier, Jérôme Alexandre, Micro-Environnement et Régulation Cellulaire Intégrée (MERCI), Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU), Laboratoire d'Oncologie Médicale, Université Paris Descartes - Paris 5 (UPD5)-Hôtel Dieu de Paris, Centre de Recherche des Cordeliers (CRC (UMR_S 872)), Université Paris Descartes - Paris 5 (UPD5)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Génomique fonctionnelle de la prolifération et différenciation cellulaire, Université Paris-Sud - Paris 11 (UP11)-Institut André Lwoff (IAL)-Centre National de la Recherche Scientifique (CNRS), We are grateful to the comité de l'Eure de la Ligue contre le Cancer and to the Association Ti'toine, for financing the fellowship of Ulrich Joimel. We thank the Groupement des Entreprises Francaises dans la Lutte contre le Cancer (GEFLUC) Rouen Normandie and the comité de Seine-Maritime de la Ligue contre le Cancer, who generously supported this work by a program grant from the Cancer Research Campaign., Université Pierre et Marie Curie - Paris 6 (UPMC)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), BMC, Ed., Micro-Environnement et Régulation Cellulaire Intégrée ( MERCI ), Université de Rouen Normandie ( UNIROUEN ), Normandie Université ( NU ) -Normandie Université ( NU ), Université Paris Descartes - Paris 5 ( UPD5 ) -Hôtel Dieu de Paris, Centre de Recherche des Cordeliers ( CRC (UMR_S 872) ), Université Pierre et Marie Curie - Paris 6 ( UPMC ) -Université Paris Descartes - Paris 5 ( UPD5 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ), and Université Paris-Sud - Paris 11 ( UP11 ) -Institut André Lwoff (IAL)-Centre National de la Recherche Scientifique ( CNRS )
Subjects: Lipopolysaccharides, Chemokine, Cancer Research, MESH : Coculture Techniques, Angiogenesis, MESH : Cytokines, medicine.medical_treatment, Fluorescent Antibody Technique, Angiogenesis Inhibitors, Apoptosis, Chick Embryo, MESH : Lipopolysaccharides, MESH : Breast Neoplasms, [ SDV.CAN ] Life Sciences [q-bio]/Cancer, 0302 clinical medicine, MESH : Chick Embryo, MESH : Female, Interferon gamma, MESH: Animals, MESH : Culture Media, Conditioned, MESH: Fluorescent Antibody Technique, Cells, Cultured, MESH : Macrophages, MESH: Angiogenesis Inhibitors, MESH: Molybdenum, 0303 health sciences, MESH: Cytokines, biology, Neovascularization, Pathologic, MESH: Culture Media, Conditioned, MESH: Enzyme-Linked Immunosorbent Assay, hemic and immune systems, MESH: Chick Embryo, lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens, MESH: Chemokines, MESH : Enzyme-Linked Immunosorbent Assay, Recombinant Proteins, MESH : Molybdenum, Endothelial stem cell, MESH: Interferon-gamma, Recombinant, Interleukin 10, Cytokine, Oncology, 030220 oncology & carcinogenesis, Cytokines, Tumor necrosis factor alpha, Female, Chemokines, medicine.drug, Research Article, MESH: Cells, Cultured, Macrophage colony-stimulating factor, Breast Neoplasms, Enzyme-Linked Immunosorbent Assay, [SDV.CAN]Life Sciences [q-bio]/Cancer, lcsh:RC254-282, MESH: Coculture Techniques, 03 medical and health sciences, Interferon-gamma, [SDV.CAN] Life Sciences [q-bio]/Cancer, MESH : Cells, Cultured, MESH : Angiogenesis Inhibitors, medicine, Genetics, Animals, Humans, MESH : Chemokines, 030304 developmental biology, Molybdenum, MESH : Interferon-gamma, Recombinant, MESH: Humans, business.industry, Macrophages, MESH: Apoptosis, MESH : Humans, MESH : Neovascularization, Pathologic, MESH: Macrophages, Coculture Techniques, MESH : Fluorescent Antibody Technique, Culture Media, Conditioned, Immunology, Cancer research, biology.protein, MESH : Animals, MESH: Lipopolysaccharides, business, MESH: Neovascularization, Pathologic, MESH: Female, MESH : Apoptosis, MESH: Breast Neoplasms
Abstract: Background Infiltration by macrophages (Mφ) indicates a poor prognosis in breast cancers, in particular by inducing angiogenesis. Our study aimed 1) to investigate the mechanism by which cooperation between Mφ and aggressive breast cancer cells (MDA-MB-231) induces angiogenesis; 2) to examine the effect of tetrathiomolybdate (TM) on this angiogenic activity. Methods Mφ coincubated with MDA-MB-231 were used as a model to mimic the inflammatory microenvironment. Angiogenesis induced by the culture media was tested in the chick chorioallantoic membrane (CAM). Mφ phenotype was evaluated by 1) expression of the M1 marker CD80, and secretion of interleukin 10 (IL-10), an M2 marker; 2) capacity to secrete Tumour Necrosis Factor α (TNFα) when stimulated by lipopolysaccharide/interferon γ (LPS/IFNγ); 3) ability to induce MDA-MB-231 apoptosis. To explore the molecular mechanisms involved, cytokine profiles of conditioned media from MDA-MB-231, Mφ and the coculture were characterised by an antibody cytokine array. All experiments were carried out both in presence and in absence of TM. Results Incubation of Mφ with MDA-MB-231 induced a pro-angiogenic effect in the CAM. It emerged that the angiogenic activity of the coculture is due to the capacity of Mφ to switch from M1 Mφ towards M2, probably due to an increase in Macrophage Colony Stimulating Factor. This M1-M2 switch was shown by a decreased expression of CD80 upon LPS/IFNγ stimulation, an increased secretion of IL-10, a decreased secretion of TNFα in response to LPS/IFNγ and an inability to potentiate apoptosis. At the molecular level, the angiogenic activity of the coculture medium can be explained by the secretion of CXC chemokines/ELR+ and CC chemokines. Although TM did not modify either the M2 phenotype in the coculture or the profile of the secreted chemokines, it did decrease the angiogenic activity of the coculture medium, suggesting that TM inhibited angiogenic activity by interfering with the endothelial cell signalling induced by these chemokines. Conclusions Cooperation between Mφ and MDA-MB-231 transformed M1 Mφ to an angiogenic, M2 phenotype, attested by secretion of CXC chemokines/ELR+ and CC chemokines. TM inhibited this coculture-induced increase in angiogenic activity, without affecting either Mφ phenotype or cytokine secretion profiles.
Published: 2010
Full Text: View/download PDF

32. Adenosine triphosphatase pontin is overexpressed in hepatocellular carcinoma and coregulated with reptin through a new posttranslational mechanism

Author: Jean Rosenbaum, Philippe Metzler, Hervé Prats, Christian Touriol, Jessica Zucman-Rossi, Paulette Bioulac-Sage, Alexandra Nicou, Patrick Lestienne, Jérémy Fernandez, Danièle Taras, Ludovic Ménard, Valérie Haurie, Charles Balabaud, Fibrose hépatique et cancer du foie, Université Bordeaux Segalen - Bordeaux 2-IFR66-Institut National de la Santé et de la Recherche Médicale ( INSERM ), Institut de médecine moléculaire de Rangueil ( I2MR ), Université Toulouse III - Paul Sabatier ( UPS ), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-IFR150-Institut National de la Santé et de la Recherche Médicale ( INSERM ), Service d'Hépato-Gastro-Entérologie, CHU Bordeaux [Bordeaux]-Hôpital Saint-André, Laboratoire d'anatomie pathologique, CHU Bordeaux [Bordeaux]-Groupe hospitalier Pellegrin, Genomique Fonctionnelle des Tumeurs Solides, Université Paris Diderot - Paris 7 ( UPD7 ) -IFR105-Université Paris Descartes - Paris 5 ( UPD5 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Université Bordeaux Segalen - Bordeaux 2-IFR66-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut de médecine moléculaire de Rangueil (I2MR), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-IFR150-Institut National de la Santé et de la Recherche Médicale (INSERM), Génomique Fonctionnelle des Tumeurs Solides (U1162), Université Paris 13 (UP13)-Université Paris Diderot - Paris 7 (UPD7)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Rosenbaum, Jean, and Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées- Institut Fédératif de Recherche Bio-médicale Institution (IFR150)-Institut National de la Santé et de la Recherche Médicale (INSERM)
Subjects: Small interfering RNA, Telomerase, MESH : Protein Biosynthesis, MESH : Liver Neoplasms, MESH : RNA, Messenger, MESH: DNA Helicases, translation, Apoptosis, 0302 clinical medicine, Ubiquitin, MESH: Liver Neoplasms, MESH : DNA Helicases, RUVBL2, Transcriptional regulation, MESH : Cell Proliferation, MESH: Carcinoma, Hepatocellular, 0303 health sciences, biology, MESH: Proteasome Endopeptidase Complex, Liver Neoplasms, Translation (biology), Cell biology, helicase, 030220 oncology & carcinogenesis, MESH: Protein Biosynthesis, MESH : Carrier Proteins, Proteasome Inhibitors, MESH : Carcinoma, Hepatocellular, Carcinoma, Hepatocellular, MESH: Carrier Proteins, [SDV.BC]Life Sciences [q-bio]/Cellular Biology, Chromatin remodeling, Article, 03 medical and health sciences, MESH: Cell Proliferation, ubiquitin, MESH : Proteasome Endopeptidase Complex, Humans, RNA, Messenger, [SDV.BC] Life Sciences [q-bio]/Cellular Biology, 030304 developmental biology, Cell Proliferation, MESH: RNA, Messenger, MESH: Humans, Hepatology, [ SDV.BC ] Life Sciences [q-bio]/Cellular Biology, MESH: Apoptosis, MESH : Humans, DNA Helicases, Molecular biology, proteasome, Proteasome, Protein Biosynthesis, biology.protein, ATPases Associated with Diverse Cellular Activities, prognosis, Carrier Proteins, MESH : Apoptosis
Abstract: International audience; Reptin and Pontin are related ATPases associated with stoichiometric amounts in several complexes involved in chromatin remodeling, transcriptional regulation, and telomerase activity. We found that Reptin was up-regulated in hepatocellular carcinoma (HCC) and that down-regulation of Reptin led to growth arrest. We show here that Pontin messenger RNA (mRNA) is also up-regulated in human HCC 3.9-fold as compared to nontumor liver (P = 0.0004). Pontin expression was a strong independent factor of poor prognosis in a multivariate analysis. As for Reptin, depletion of Pontin in HuH7 cells with small interfering RNAs (siRNAs) led to growth arrest. Remarkably, Pontin depletion led to down-regulation of Reptin as shown with western blot, and vice versa. Whereas siRNAs induced a decrease of their cognate mRNA targets, they did not affect the transcripts of the partner protein. Translation of Pontin or Reptin was not altered when the partner protein was silenced. However, pulse-chase experiments demonstrated that newly synthesized Pontin or Reptin stability was reduced in Reptin- or Pontin-depleted cells, respectively. This phenomenon was reversed upon inhibition of proteasome or ubiquitin-activating enzyme (E1). In addition, proteasome inhibition could partly restore Pontin steady-state levels in Reptin-depleted cells, as shown by western blot. This restoration was not observed when cells were also treated with cycloheximide, thus confirming that proteasomal degradation in this setting was restricted to newly synthesized Pontin. CONCLUSION: Reptin and Pontin protein levels are strictly controlled by a posttranslational mechanism involving proteasomal degradation of newly synthesized proteins. These data demonstrate a tight regulatory and reciprocal interaction between Reptin and Pontin, which may in turn lead to the maintenance of their 1:1 stoichiometry.
Published: 2009
Full Text: View/download PDF

33. Pulmonary effects of keratinocyte growth factor in newborn rats exposed to hyperoxia.: KGF effects in hyperoxia-exposed rat pups

Author: Franco-Montoya, Marie-Laure, Bourbon, Jacques, Durrmeyer, Xavier, Lorotte, Stephanie, Jarreau, Pierre-Henri, Delacourt, Christophe, Institut Mondor de Recherche Biomédicale (IMRB), Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), PremUp Foundation, Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Université Paris Descartes - Paris 5 (UPD5)-CHI Créteil-Institut de Recherche pour le Développement (IRD)-Université Paris-Sud - Paris 11 (UP11)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Université Paris Diderot - Paris 7 (UPD7), Service de réanimation néonatale de Créteil, CHI Créteil, Service de réanimation néonatale Port-Royal, Hôpital Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Institut de Recherche pour le Développement (IRD)-Université Paris-Sud - Paris 11 (UP11)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Université Paris Diderot - Paris 7 (UPD7)-CHI Créteil-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut Mondor de Recherche Biomédicale ( IMRB ), Institut National de la Santé et de la Recherche Médicale ( INSERM ) -IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 ( UPEC UP12 ), Institut de Recherche pour le Développement ( IRD ) -Université Paris-Sud - Paris 11 ( UP11 ) -Université Pierre et Marie Curie - Paris 6 ( UPMC ) -Université Paris Diderot - Paris 7 ( UPD7 ) -CHI Créteil-Université Paris Descartes - Paris 5 ( UPD5 ) -Sorbonne Universités-Institut National de la Santé et de la Recherche Médicale ( INSERM ), and CHU Cochin [AP-HP]
Subjects: MESH: Pulmonary Surfactant-Associated Protein B, MESH: Pulmonary Alveoli, lung protection, MESH : DNA, MESH: Rats, Sprague-Dawley, MESH: Animals, Newborn, MESH: Pregnancy, developing lung, MESH : Receptor, Epidermal Growth Factor, MESH : Cell Proliferation, MESH: CCAAT-Enhancer-Binding Protein-alpha, MESH : CCAAT-Enhancer-Binding Protein-alpha, MESH : Female, MESH: Animals, MESH : Fibroblast Growth Factor 7, MESH : Bronchoalveolar Lavage Fluid, MESH : Gene Expression Regulation, MESH : Rats, MESH : Animals, Newborn, MESH: DNA, respiratory system, MESH: Gene Expression Regulation, MESH: Survival Analysis, MESH : Hyperoxia, MESH: Cell Adhesion Molecules, MESH: Rats, MESH : Lung, MESH : Transforming Growth Factor alpha, MESH: Transforming Growth Factor alpha, MESH: Receptor, Epidermal Growth Factor, MESH : Phospholipids, MESH : Cell Adhesion Molecules, MESH: Hyperoxia, MESH: Cell Proliferation, bronchopulmonary dysplasia, MESH: Lung, [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology, alveolar epithelial cell, [ SDV.BBM ] Life Sciences [q-bio]/Biochemistry, Molecular Biology, MESH: Phospholipids, MESH: Humans, MESH: Bronchoalveolar Lavage Fluid, MESH: Apoptosis, MESH : Humans, lung inflammation, MESH: Fibroblast Growth Factor 7, MESH : Rats, Sprague-Dawley, respiratory tract diseases, MESH : Pregnancy, MESH : Animals, MESH : Survival Analysis, MESH : Pulmonary Alveoli, MESH : Pulmonary Surfactant-Associated Protein B, MESH: Female, MESH : Apoptosis
Abstract: International audience; Acute lung injury and compromised alveolar development characterize bronchopulmonary dysplasia (BPD) of the premature neonate. High levels of keratinocyte growth factor (KGF), a cell-cell mediator with pleiotrophic lung effects, are associated with low BPD risk. KGF decreases mortality in hyperoxia-exposed newborn rodents, a classic model of injury-induced impaired alveolarization, although the pulmonary mechanisms of this protection are poorly defined. These were explored through in vitro and in vivo approaches in the rat. Hyperoxia decreased by 30% the rate of wound closure of a monolayer of fetal alveolar epithelial cells, due to cell death, which was overcome by recombinant human KGF (100 ng/ml). In rat pups exposed to >95% O2 from birth, increased viability induced by intraperitoneal injection of KGF (2 microg/g body wt) every other day was associated with prevention of neutrophil influx in bronchoalveolar lavage (BAL), prevention of decreases in whole lung DNA content and cell proliferation rate, partial prevention of apoptosis increase, and a markedly increased proportion of surfactant protein B-immunoreactive cells in lung parenchyma. Increased lung antioxidant capacity is likely to be due in part to enhanced CAAT/enhancer binding protein alpha expression. By contrast, KGF neither corrected changes induced by hyperoxia in parameters of lung morphometry that clearly indicated impaired alveolarization nor had any significant effect on tissue or BAL surfactant phospholipids. These findings evidence KGF alveolar epithelial cell protection, enhancing effects on alveolar repair capacity, and anti-inflammatory effects in the injured neonatal lung that may account, at least in part, for its ability to reduce mortality. They argue in favor of a therapeutic potential of KGF in the injured neonatal lung.
Published: 2009
Full Text: View/download PDF

34. TRPC1 is regulated by caveolin-1 and is involved in oxidized LDL-induced apoptosis of vascular smooth muscle cells

Author: Bertrand Marcheix, Cécile Vindis, Cécile Ingueneau, Anne Nègre-Salvayre, Anne Athias, Robert Salvayre, Philippe Gambert, Uyen Huynh-Do, Institut de médecine moléculaire de Rangueil ( I2MR ), Université Paul Sabatier - Toulouse 3 ( UPS ) -IFR31-IFR150-Institut National de la Santé et de la Recherche Médicale ( INSERM ), Departement of Nephrology and Hypertension, and Department of Clinical research, University of Bern, Plateforme Lipidomique [Dijon] ( LAP ), Lipides - Nutrition - Cancer (U866) ( LNC ), Université de Bourgogne ( UB ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Ecole Nationale Supérieure de Biologie Appliquée à la Nutrition et à l'Alimentation de Dijon ( ENSBANA ) -Université de Bourgogne ( UB ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Ecole Nationale Supérieure de Biologie Appliquée à la Nutrition et à l'Alimentation de Dijon ( ENSBANA ) -IFR100 - Structure fédérative de recherche Santé-STIC-Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand ( CHU Dijon ), Institut de médecine moléculaire de Rangueil (I2MR), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées- Institut Fédératif de Recherche Bio-médicale Institution (IFR150)-Institut National de la Santé et de la Recherche Médicale (INSERM), Plateforme Lipidomique [Dijon] (LAP), Lipides - Nutrition - Cancer (U866) (LNC), Université de Bourgogne (UB)-Institut National de la Santé et de la Recherche Médicale (INSERM)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Ecole Nationale Supérieure de Biologie Appliquée à la Nutrition et à l'Alimentation de Dijon (ENSBANA)-Université de Bourgogne (UB)-Institut National de la Santé et de la Recherche Médicale (INSERM)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Ecole Nationale Supérieure de Biologie Appliquée à la Nutrition et à l'Alimentation de Dijon (ENSBANA)-IFR100 - Structure fédérative de recherche Santé-STIC-Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), and Simon, Marie Francoise
Subjects: MESH: Lipoproteins, LDL, Vascular smooth muscle, Oxysterol, Caveolin 1, Apoptosis, Biology, MESH: Base Sequence, MESH : RNA, Small Interfering, Muscle, Smooth, Vascular, TRPC1, Transient receptor potential channel, MESH: RNA, Small Interfering, MESH : Cells, Cultured, Humans, MESH: Caveolin 1, RNA, Small Interfering, MESH: TRPC Cation Channels, Cells, Cultured, TRPC Cation Channels, MESH: Humans, Base Sequence, MESH : Gene Expression Regulation, MESH: Apoptosis, MESH : Humans, MESH : TRPC Cation Channels, MESH : Muscle, Smooth, Vascular, Articles, Cell Biology, MESH: Muscle, Smooth, Vascular, Actin cytoskeleton, MESH: Gene Expression Regulation, Cell biology, Lipoproteins, LDL, Gene Expression Regulation, MESH : Caveolin 1, Molecular Medicine, lipids (amino acids, peptides, and proteins), MESH : Base Sequence, MESH : Lipoproteins, LDL, Homeostasis, MESH : Apoptosis, MESH: Cells, Cultured
Abstract: International audience; Oxidized low-density lipoprotein (oxLDL) induced-apoptosis of vascular cells may participate in plaque instability and rupture. We have previously shown that vascular smooth muscle cells (VSMC) stably expressing caveolin-1 were more susceptible to oxLDL-induced apoptosis than VSMC expressing lower level of caveolin-1, and this was correlated with enhanced Ca(2+) entry and pro-apoptotic events. In this study, we aimed to identify the molecular events involved in oxLDL-induced Ca(2+) influx and their regulation by the structural protein caveolin-1. In VSMC, transient receptor potential canonical-1 (TRPC1) silencing by ARN interference prevents the Ca(2+) influx and reduces the toxicity induced by oxLDL. Moreover, caveolin-1 silencing induces concomitant decrease of TRPC1 expression and reduces oxLDL-induced apoptosis of VSMC. OxLDL enhanced the cell surface expression of TRPC1, as shown by biotinylation of cell surface proteins, and induced TRPC1 translocation into caveolar compartment, as assessed by subcellular fractionation. OxLDL-induced TRPC1 translocation was dependent on actin cytoskeleton and associated with a dramatic rise of 7-ketocholesterol (a major oxysterol in oxLDL) into caveolar membranes, whereas the caveolar content of cholesterol was unchanged. Altogether, the reported results show that TRPC1 channels play a role in Ca(2+) influx and Ca(2+) homeostasis deregulation that mediate apoptosis induced by oxLDL. These data also shed new light on the role of caveolin-1 and caveolar compartment as important regulators of TRPC1 trafficking to the plasma membrane and apoptotic processes that play a major role in atherosclerosis.
Published: 2009

35. Spatiotemporal activation of caspase-dependent and -independent pathways in staurosporine-induced apoptosis of p53wt and p53mt human cervical carcinoma cells

Author: Jean-Luc Prétet, Sophie Launay, Christiane Mougin, Magali Nicolier, Anne-Zélie Decrion-Barthod, Carcinogénèse épithéliale : facteurs prédictifs et pronostiques - UFC (EA 3181) (CEF2P / CARCINO), Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC)-Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon), Santé - STIC, Université de Bourgogne (UB)-Institut National de la Santé et de la Recherche Médicale (INSERM), Carcinogénèse épithéliale : facteurs prédictifs et pronostiques - UFC ( CEF2P / CARCINO ), Centre Hospitalier Régional Universitaire [Besançon] ( CHRU Besançon ) -Université Bourgogne Franche-Comté ( UBFC ) -Université de Franche-Comté ( UFC ), and Université de Bourgogne ( UB ) -Institut National de la Santé et de la Recherche Médicale ( INSERM )
Subjects: MESH: Carcinoma, MESH: Signal Transduction, MESH : Staurosporine, Uterine Cervical Neoplasms, Apoptosis, Mitochondrial apoptosis-induced channel, [ SDV.CAN ] Life Sciences [q-bio]/Cancer, HeLa, 0302 clinical medicine, Staurosporine, MESH : Female, MESH: Tumor Suppressor Protein p53, Caspase, 0303 health sciences, biology, MESH : Carcinoma, Cytochrome c, General Medicine, Caspase Inhibitors, Cell biology, MESH: Uterine Cervical Neoplasms, MESH : Antineoplastic Agents, Caspases, 030220 oncology & carcinogenesis, DNA fragmentation, Female, MESH : Mutation, Signal Transduction, medicine.drug, Programmed cell death, MESH: Enzyme Activation, MESH: Mutation, MESH : Uterine Cervical Neoplasms, Antineoplastic Agents, [SDV.CAN]Life Sciences [q-bio]/Cancer, 03 medical and health sciences, medicine, Humans, 030304 developmental biology, MESH : Signal Transduction, MESH: Caspases, MESH: Humans, MESH: Apoptosis, Carcinoma, MESH : Humans, Cell Biology, biology.organism_classification, Enzyme Activation, MESH : Tumor Suppressor Protein p53, Mutation, Cancer research, biology.protein, MESH: Staurosporine, MESH: Antineoplastic Agents, Tumor Suppressor Protein p53, MESH : Caspases, MESH : Enzyme Activation, MESH: Female, MESH : Apoptosis
Abstract: International audience; BACKGROUND INFORMATION: Caspase-dependent and -independent death mechanisms are involved in apoptosis in a variety of human carcinoma cells treated with antineoplastic compounds. Our laboratory has reported that p53 is a key contributor of mitochondrial apoptosis in cervical carcinoma cells after staurosporine exposure. However, higher mitochondrial membrane potential dissipation and greater DNA fragmentation were observed in p53wt (wild-type p53) HeLa cells compared with p53mt (mutated p53) C-33A cells. Here, we have studied events linked to the mitochondrial apoptotic pathway. RESULTS: Staurosporine can induce death of HeLa cells via a cytochrome c/caspase-9/caspase-3 mitochondrial-dependent apoptotic pathway and via a delayed caspase-independent pathway. In contrast with p53wt cells, p53mt C-33A cells exhibit firstly caspase-8 activation leading to caspase-3 activation and Bid cleavage followed by cytochrome c release. Attenuation of PARP-1 [poly(ADP-ribose) polymerase-1] cleavage as well as oligonucleosomal DNA fragmentation in the presence of z-VAD-fmk points toward a major involvement of a caspase-dependent pathway in staurosporine-induced apoptosis in p53wt HeLa cells, which is not the case in p53mt C-33A cells. Meanwhile, the use of 3-aminobenzamide, a PARP-1 inhibitor known to prevent AIF (apoptosis-inducing factor) release, significantly decreases staurosporine-induced death in these p53mt carcinoma cells, suggesting a preferential implication of caspase-independent apoptosis. On the other hand, we show that p53, whose activity is modulated by pifithrin-alpha, isolated as a suppressor of p53-mediated transactivation, or by PRIMA-1 (p53 reactivation and induction of massive apoptosis), that reactivates mutant p53, causes cytochrome c release as well as mitochondrio-nuclear AIF translocation in staurosporine-induced apoptosis of cervical carcinoma cells. CONCLUSIONS: The present paper highlights that staurosporine engages the intrinsic mitochondrial apoptotic pathway via caspase-8 or caspase-9 signalling cascades and via caspase-independent cell death, as well as through p53 activity.
Published: 2009
Full Text: View/download PDF

36. Molecular crosstalk between TRAIL and natural antioxidants in the treatment of cancer

Author: Olivier Micheau, Stuart A. Rushworth, School of Chemical Sciences and Pharmacy, University of East Anglia [Norwich] (UEA), Lipides - Nutrition - Cancer (U866) (LNC), Université de Bourgogne (UB)-Institut National de la Santé et de la Recherche Médicale (INSERM)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Ecole Nationale Supérieure de Biologie Appliquée à la Nutrition et à l'Alimentation de Dijon (ENSBANA), University of East Anglia [Norwich] ( UEA ), Lipides - Nutrition - Cancer (U866) ( LNC ), Université de Bourgogne ( UB ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Ecole Nationale Supérieure de Biologie Appliquée à la Nutrition et à l'Alimentation de Dijon ( ENSBANA ), and Micheau, Olivier
Subjects: medicine.medical_treatment, MESH : Reactive Oxygen Species, TRAIL, Resveratrol, wogonin, MESH: Drug Synergism, MESH : TNF-Related Apoptosis-Inducing Ligand, chemistry.chemical_compound, 0302 clinical medicine, MESH: Up-Regulation, MESH: Tumor Suppressor Protein p53, MESH : Up-Regulation, 0303 health sciences, apoptosis, MESH: Reactive Oxygen Species, ROS, 3. Good health, MESH: Flavanones, MESH : Antineoplastic Agents, Cytokine, antioxidants, cell death, 030220 oncology & carcinogenesis, MESH : Proto-Oncogene Proteins, MESH : Antioxidants, MESH : Apoptosis Regulatory Proteins, flavonoid, MESH: TNF-Related Apoptosis-Inducing Ligand, Programmed cell death, MESH: Cell Line, Tumor, MESH : Drug Synergism, Biology, 03 medical and health sciences, Wogonin, [SDV.BBM] Life Sciences [q-bio]/Biochemistry, Molecular Biology, medicine, [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology, [ SDV.BBM ] Life Sciences [q-bio]/Biochemistry, Molecular Biology, 030304 developmental biology, Pharmacology, MESH: Humans, MESH : Cell Line, Tumor, tumour, MESH: Apoptosis Regulatory Proteins, MESH : Flavanones, MESH: Apoptosis, MESH : Humans, MESH: Antioxidants, Baicalein, MESH: Proto-Oncogene Proteins, MESH : Tumor Suppressor Protein p53, chemistry, Apoptosis, Cancer cell, Immunology, Cancer research, Curcumin, MESH: Antineoplastic Agents, MESH : Apoptosis
Abstract: International audience; The endogenous protein, tumour necrosis factor receptor apoptosis-inducing ligand (TRAIL), induces apoptosis in a wide variety of transformed and cancer cells but has little or no effect on normal cells. Therefore, TRAIL is considered to be a tumour-selective, apoptosis-inducing cytokine and a promising new candidate for cancer prevention and treatment. Some cancer cells are however resistant to TRAIL-induced apoptosis, but treatment in combination with conventional chemotherapeutic drugs or radiation generally restores TRAIL sensitivity in those cells. A novel class of molecules exhibiting synergy with TRAIL but devoid of major side effects are emerging as alternative approaches to treat resistant cancer cells, including natural antioxidants such as sulphoraphane or the flavonoids curcumin, quercetin, resveratrol, baicalein and wogonin. In this issue of the BJP, Lee et al. demonstrate that treatment of TRAIL-resistant cancer cells with wogonin restores TRAIL-induced cell death in a reactive oxygen species-dependent manner through up-regulation of p53 and Puma.
Published: 2009
Full Text: View/download PDF

37. iNKT cell development is orchestrated by different branches of TGF-beta signaling

Author: Sylvie Martel, C Garcia, Régine Losson, Jean-Marc Doisne, Farhan S. Cyprian, Nadia Duarte, Kamel Benlagha, Kai-Ping Yan, Jean-Benoît Le Luduec, Laurent Bartholin, Julien C. Marie, Branka Horvat, David F. Vincent, Ruth Rimokh, Hôpital Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Immunologie, génétique et traitement des maladies métaboliques et du diabète (UMR_S 561), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Oncogénèse et progression tumorale, Centre Léon Bérard [Lyon]-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut de génétique et biologie moléculaire et cellulaire (IGBMC), Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Louis Pasteur - Strasbourg I, Virologie humaine, École normale supérieure - Lyon (ENS Lyon)-IFR128-Institut National de la Santé et de la Recherche Médicale (INSERM), Immunité infection vaccination (I2V), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-IFR128-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut de biologie et chimie des protéines [Lyon] (IBCP), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS), Université Louis Pasteur - Strasbourg I-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), École normale supérieure de Lyon (ENS de Lyon)-IFR128-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Cochin [AP-HP], Immunologie, génétique et traitement des maladies métaboliques et du diabète ( UMR_S 561 ), Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Université Paris Descartes - Paris 5 ( UPD5 ), Centre Léon Bérard [Lyon]-Université Claude Bernard Lyon 1 ( UCBL ), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale ( INSERM ), Institut de génétique et biologie moléculaire et cellulaire ( IGBMC ), Université Louis Pasteur - Strasbourg I-Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ), École normale supérieure - Lyon ( ENS Lyon ) -IFR128-Institut National de la Santé et de la Recherche Médicale ( INSERM ), Immunité infection vaccination ( I2V ), Université Claude Bernard Lyon 1 ( UCBL ), Université de Lyon-Université de Lyon-IFR128-Institut National de la Santé et de la Recherche Médicale ( INSERM ), Institut de biologie et chimie des protéines [Lyon] ( IBCP ), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique ( CNRS ), and Peney, Maité
Subjects: MESH: Signal Transduction, MESH : Transcription Factors, MESH : Receptors, Transforming Growth Factor beta, MESH: Spleen, Cellular differentiation, Apoptosis, MESH: T-Lymphocyte Subsets, Mice, 0302 clinical medicine, T-Lymphocyte Subsets, Transforming Growth Factor beta, MESH: Smad4 Protein, Immunology and Allergy, MESH: Animals, Smad4 Protein, 0303 health sciences, biology, Stem Cells, Cell Differentiation, MESH: Transcription Factors, Natural killer T cell, MESH : Mice, Transgenic, Cell biology, MESH: Interleukin-2 Receptor beta Subunit, MESH : Stem Cells, MESH: Receptors, Transforming Growth Factor beta, Stem cell, Signal transduction, MESH : Cell Differentiation, Signal Transduction, MESH : Spleen, MESH: Cell Differentiation, MESH: T-Box Domain Proteins, MESH: Mice, Transgenic, Immunology, MESH : Cell Lineage, Mice, Transgenic, MESH: Stem Cells, Article, 03 medical and health sciences, MESH : Mice, TGF beta signaling pathway, Animals, Cell Lineage, Transcription factor, MESH: Mice, MESH: Transforming Growth Factor beta, MESH : Interleukin-2 Receptor beta Subunit, 030304 developmental biology, MESH : Signal Transduction, Cell growth, MESH: Apoptosis, MESH : Smad4 Protein, Transforming growth factor beta, MESH: Cell Lineage, MESH : Natural Killer T-Cells, MESH : T-Lymphocyte Subsets, Interleukin-2 Receptor beta Subunit, MESH : T-Box Domain Proteins, MESH : Transforming Growth Factor beta, MESH: Natural Killer T-Cells, biology.protein, Natural Killer T-Cells, MESH : Animals, T-Box Domain Proteins, Receptors, Transforming Growth Factor beta, Spleen, MESH : Apoptosis, Transcription Factors, 030215 immunology
Abstract: International audience; Invariant natural killer T (iNKT) cells constitute a distinct subset of T lymphocytes exhibiting important immune-regulatory functions. Although various steps of their differentiation have been well characterized, the factors controlling their development remain poorly documented. Here, we show that TGF-beta controls the differentiation program of iNKT cells. We demonstrate that TGF-beta signaling carefully and specifically orchestrates several steps of iNKT cell development. In vivo, this multifaceted role of TGF-beta involves the concerted action of different pathways of TGF-beta signaling. Whereas the Tif-1gamma branch controls lineage expansion, the Smad4 branch maintains the maturation stage that is initially repressed by a Tif-1gamma/Smad4-independent branch. Thus, these three different branches of TGF-beta signaling function in concert as complementary effectors, allowing TGF-beta to fine tune the iNKT cell differentiation program.
Published: 2009
Full Text: View/download PDF

38. Lysosomal serine protease CLN2 regulates tumor necrosis factor-alpha-mediated apoptosis in a Bid-dependent manner

Author: Nathalie Andrieu-Abadie, Virginie Garcia, Hélène Autefage, Nicole Therville, Thierry Levade, Marie-Françoise Altié, Catherine Caillaud, Virginie Albinet, Hortense Berges, Marie-Laure Nicolau, Institut de médecine moléculaire de Rangueil ( I2MR ), Université Toulouse III - Paul Sabatier ( UPS ), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-IFR150-Institut National de la Santé et de la Recherche Médicale ( INSERM ), Institut Cochin ( UMR_S567 / UMR 8104 ), Université Paris Descartes - Paris 5 ( UPD5 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ), Laboratoire de Biochimie [Purpan], Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-CHU Toulouse [Toulouse]-Institut Fédératif de Biologie (IFB) - Hôpital Purpan, Hôpital Purpan [Toulouse], CHU Toulouse [Toulouse]-CHU Toulouse [Toulouse]-Hôpital Purpan [Toulouse], CHU Toulouse [Toulouse], Institut de médecine moléculaire de Rangueil (I2MR), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées- Institut Fédératif de Recherche Bio-médicale Institution (IFR150)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut Cochin (UMR_S567 / UMR 8104), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Laboratoire de Biochimie [CHU Toulouse], Institut Fédératif de Biologie (IFB), Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Pôle Biologie [CHU Toulouse], Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), and Simon, Marie Francoise
Subjects: Small interfering RNA, MESH : Cytochromes c, MESH: Neurons, MESH: Cricetinae, Apoptosis, MESH: Caspase 9, Biochemistry, Aminopeptidases, MESH: Recombinant Proteins, MESH: Cricetulus, Cricetinae, MESH: Caspase 3, MESH : CHO Cells, MESH : Catalysis, MESH: Animals, MESH : Caspase 3, MESH: Endopeptidases, Caspase, Neurons, MESH : Tumor Necrosis Factor-alpha, biology, Tripeptidyl-Peptidase 1, MESH : Caspase 9, Caspase 3, Mechanisms of Signal Transduction, MESH : Cricetinae, Cytochromes c, Transfection, MESH: Cytochromes c, Caspase 9, Recombinant Proteins, MESH : Endopeptidases, Cell biology, Tumor necrosis factor alpha, BH3 Interacting Domain Death Agonist Protein, Programmed cell death, Proteases, MESH : Recombinant Proteins, MESH : Cricetulus, MESH: BH3 Interacting Domain Death Agonist Protein, CHO Cells, Catalysis, MESH : Neurons, Cricetulus, MESH: CHO Cells, Endopeptidases, MESH : Fibroblasts, Animals, Humans, MESH : BH3 Interacting Domain Death Agonist Protein, Dipeptidyl-Peptidases and Tripeptidyl-Peptidases, Molecular Biology, Serine protease, MESH: Humans, Tumor Necrosis Factor-alpha, MESH: Apoptosis, MESH : Humans, Cell Biology, Fibroblasts, MESH : Lysosomes, MESH: Catalysis, Molecular biology, MESH: Fibroblasts, MESH: Tumor Necrosis Factor-alpha, biology.protein, MESH : Animals, Serine Proteases, Lysosomes, MESH : Apoptosis, MESH: Lysosomes
Abstract: International audience; Apoptosis is a highly organized, energy-dependent program by which multicellular organisms eliminate damaged, superfluous, and potentially harmful cells. Although caspases are the most prominent group of proteases involved in the apoptotic process, the role of lysosomes has only recently been unmasked. This study investigated the role of the lysosomal serine protease CLN2 in apoptosis. We report that cells isolated from patients affected with late infantile neuronal ceroid lipofuscinosis (LINCL) having a deficient activity of CLN2 are resistant to the toxic effect of death ligands such as tumor necrosis factor (TNF), CD95 ligand, or tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) but not to receptor-independent stress agents. CLN2-deficient cells exhibited a defect in TNF-induced Bid cleavage, release of cytochrome c, and caspase-9 and -3 activation. Moreover, extracts from CLN2-overexpressing cells or a CLN2 recombinant protein were able to catalyze the in vitro cleavage of Bid. Noteworthy, correction of the lysosomal enzyme defect of LINCL fibroblasts using a medium enriched in CLN2 protein enabled restoration of TNF-induced Bid and caspase-3 processing and toxicity. Conversely, transfection of CLN2-corrected cells with small interfering RNA targeting Bid abrogated TNF-induced cell death. Altogether, our study demonstrates that genetic deletion of the lysosomal serine protease CLN2 and the subsequent loss of its catalytic function confer resistance to TNF in non-neuronal somatic cells, indicating that CLN2 plays a yet unsuspected role in TNF-induced cell death.
Published: 2009
Full Text: View/download PDF

39. Guidelines for the use and interpretation of assays for monitoring cell death in higher eukaryotes

Author: Aaron Ciechanover, Eric H. Baehrecke, Josef M. Penninger, Moshe Oren, Marja Jäättelä, Cecília M. P. Rodrigues, Seamus J. Martin, Lorenzo Galluzzi, Dale E. Bredesen, Stuart A. Aaronson, Donald W. Nicholson, Frank Madeo, Mikhail V. Blagosklonny, Gabriel Núñez, Hans-Uwe Simon, Adi Kimchi, Karen H. Vousden, Yoshihide Tsujimoto, David W. Andrews, Simone Fulda, J. Tschopp, John M. Abrams, Hinrich Gronemeyer, Nicolas G. Bazan, Michael O. Hengartner, Richard A. Flavell, Beth Levine, Thomas Rudel, Ilio Vitale, Eugenia Morselli, Rosario Rizzuto, Boris Zhivotovsky, Douglas R. Green, J. M. Hardwick, Maria Castedo, Guido Kroemer, Pierluigi Nicotera, Christoph Borner, David C. Rubinsztein, Junying Yuan, Jan Paul Medema, Oliver Kepp, Carmen Garrido, V De Laurenzi, Jean-Christophe Marine, Richard J. Youle, Hidenori Ichijo, Daniel J. Klionsky, Hamsa Puthalakath, Ute M. Moll, Shigekazu Nagata, R De Maria, Pierre Golstein, Marie-Lise Gougeon, Mohanish Deshmukh, Enrico Lugli, Brian David Dynlacht, Emad S. Alnemri, John A. Cidlowski, Luca Scorrano, Stuart A. Lipton, Hermann Steller, Sally Kornbluth, Gerry Melino, György Hajnóczky, Gabriel A. Rabinovich, Peter Vandenabeele, Gerald M. Cohen, Shazib Pervaiz, Marcus E. Peter, Richard A. Knight, Jochen H. M. Prehn, Sharad Kumar, Klas Blomgren, Walter Malorni, Wafik S. El-Deiry, Patrick Mehlen, Mauro Piacentini, Catherine Brenner, Apoptose, cancer et immunité (U848), Université Paris-Sud - Paris 11 (UP11)-Institut Gustave Roussy (IGR)-Institut National de la Santé et de la Recherche Médicale (INSERM), Department of Oncological Sciences, Icahn School of Medicine at Mount Sinai [New York] (MSSM), Department of Cell Biology, University of Texas Southwestern Medical Center [Dallas], Department of Biochemistry and Molecular Biology, Thomas Jefferson University-Sidney Kimmel Cancer Center, Jefferson (Philadelphia University + Thomas Jefferson University)-Jefferson (Philadelphia University + Thomas Jefferson University), Department of Biochemistry and Biomedical Sciences, McMaster University [Hamilton, Ontario], Department of Cancer Biology, University of Massachusetts Medical School [Worcester] (UMASS), University of Massachusetts System (UMASS)-University of Massachusetts System (UMASS), Neuroscience Center of Excellence, LSU Health Sciences Center, Roswell Park Cancer Institute [Buffalo] (RPCI), Center for Brain Repair and Rehabilitation, Institute of Neuroscience and Physiology [Göteborg]-University of Gothenburg (GU), Department of Pediatric Oncology, The Queen Silvia Children's Hospital, Institute of Molecular Medicine and Cell Research (ZBMZ), University of Freiburg [Freiburg], Buck Institute for Age Research, Laboratoire de génétique et biologie cellulaire (LGBC), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-École Pratique des Hautes Études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL), National Institutes of Environmental Health Sciences, National Institutes of Health [Bethesda] (NIH), Vascular and Tumor Biology Research Center, Israel Institute of Technology, Toxicology Unit, University of Leicester, Dipartimento di Scienze Biomediche, Università degli studi 'G. d'Annunzio' Chieti-Pescara [Chieti-Pescara] (Ud'A), Department of Hematology, Oncology and Molecular Medicine, Istituto Superiore di Sanità (ISS), Mediterranean Institute of Oncology, Department of Cell and Developmental Biology, University of North Carolina [Chapel Hill] (UNC), University of North Carolina System (UNC)-University of North Carolina System (UNC), Department of Pathology, New York University School of Medicine, NYU System (NYU)-NYU System (NYU), Hematology-Oncology Division, Perelman School of Medicine, University of Pennsylvania-University of Pennsylvania, Section of Immunobiology, Yale School of Medicine [New Haven, Connecticut] (YSM), Howard Hughes Medical Institute [Chevy Chase] (HHMI), Howard Hughes Medical Institute (HHMI), University Children's Hospital, Lipides - Nutrition - Cancer (U866) (LNC), Université de Bourgogne (UB)-Institut National de la Santé et de la Recherche Médicale (INSERM)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Ecole Nationale Supérieure de Biologie Appliquée à la Nutrition et à l'Alimentation de Dijon (ENSBANA), Centre d'Immunologie de Marseille - Luminy (CIML), Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Immunité Antivirale, Biothérapie et Vaccins, Institut Pasteur [Paris] (IP)-Institut National de la Santé et de la Recherche Médicale (INSERM), Department of Immunology, St Jude Children's Research Hospital, Institut de Génétique et de Biologie Moléculaire et Cellulaire (IGBMC), Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Department of Pathology, Anatomy and Cell Biology, Thomas Jefferson University, Department of Pharmacology and Molecular Sciences, Johns Hopkins University (JHU), Institute of Molecular Biology, Universität Zürich [Zürich] = University of Zurich (UZH), Graduate School of Medecine, The University of Tokyo (UTokyo), Danish Cancer Society, Institute of Cancer Biology, Department of Molecular Genetics, Weizmann Institute of Science [Rehovot, Israël], Life Sciences Institute and Department of Molecular, Cellular, and Developmental Biology and Biological Chemistry, University of Michigan [Ann Arbor], University of Michigan System-University of Michigan System, Institute of Child Health [London], University College of London [London] (UCL), Duke University School of Medicine, Centre for Cancer Biology, Hanson Institute, Adelaide, Burnham Institute for Medical Research, The Salk Institute for Biological Studies, The Scripps Research Institute [La Jolla, San Diego], University of California [San Diego] (UC San Diego), University of California (UC), Immunotechnology Section, Vaccine Research Center, National Institutes of Health [Bethesda] (NIH)-National Institute of Allergy and Infectious Diseases, Institute of Molecular Biosciences, Karl-Franzens-Universität Graz, Department of Therapeutic Research and Medicines Evaluation, Laboratory for Molecular Cancer Biology, VIB-UGent, Department for Molecular Biology, Universiteit Gent = Ghent University (UGENT), Department of Genetics, Trinity College Dublin, Center for Experimental and Molecular Medicine, Academic Medical Center - Academisch Medisch Centrum [Amsterdam] (AMC), University of Amsterdam [Amsterdam] (UvA)-University of Amsterdam [Amsterdam] (UvA), University of Amsterdam [Amsterdam] (UvA), Apoptosis, Cancer, and Development Laboratory, Centre Léon Bérard [Lyon], Apoptose Cancer et Développement, Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS), Department of Experimental Medicine and Biochemical Sciences, Università degli Studi di Roma Tor Vergata [Roma], Stony Brook University [SUNY] (SBU), State University of New York (SUNY)-State University of New York (SUNY), Department of Molecular Oncology, Göttingen Center of Molecular Biosciences, Faculty of Medicine, Georg-August-University = Georg-August-Universität Göttingen, Fujitsu Laboratories LTD., Fujitsu Laboratories Ltd., Department of Medical Chemistry, Kyoto University-Graduate School of Medicine, Merck & Co. Inc, University of Michigan Medical School [Ann Arbor], Department of Molecular Cell Biology [Rehovot], Institute of Molecular Biotechnology, Austrian Academy of Sciences (OeAW), Department of Physiology, National University of Singapore (NUS)-Yong Loo Lin School of Medicine-Graduate School for Integrative Sciences and Engineering, Singapore-MIT Alliance for Research and Technology (SMART), Massachusetts Institute of Technology (MIT), Duke-NUS Medical School [Singapore], Ben May Department for Cancer Research, University of Chicago-Ben May Department for Cancer Research, Laboratory of Cell Biology, National Institute for Infectious Diseases IRCCS 'L. Spallanzani', Department of Biology, Department of Physiology and Medical Physics, Royal College of Surgeons in Ireland (RCSI), Department of Biochemistry, La Trobe University [Melbourne], Laboratorie de Inmunopatologia, Instituto de Biología y Medicina Experimental [Buenos Aires] (IBYME), Consejo Nacional de Investigaciones Científicas y Técnicas [Buenos Aires] (CONICET)-Consejo Nacional de Investigaciones Científicas y Técnicas [Buenos Aires] (CONICET), Department of Biomedical Sciences, Università degli Studi di Padova = University of Padua (Unipd), iMed.UL, Universidade de Lisboa = University of Lisbon (ULISBOA), Cambridge Institute for Medical Research (CIMR), University of Cambridge [UK] (CAM), Biocenter, Julius-Maximilians-Universität Würzburg (JMU), Department of Cell Physiology and Metabolism, University of Geneva Medical School, Dulbecco-Telethon Institute, Venetian Institute Molecular Medicine (VIMM), University of Bern, Laboratory of Apoptosis and Cancer Biology, Rockefeller University [New York], Department of Biochemistry [Lausanne], Université de Lausanne = University of Lausanne (UNIL), Department of Medical Genetics, Osaka University Medical School, Department for Molecular Biomedical Research, The Beatson Institute for Cancer Research, University of Glasgow, Biochemistry Section, Surgical Neurology Branch, National Institutes of Health [Bethesda] (NIH)-National Institute of Neurological Disorders and Stroke, Department of cell biology, Harvard Medical School [Boston] (HMS), Division of Toxicology, karolinska institute-Institute of Environmental Medicine, Scorrano, Luca, Tschopp, Jean-Marie, Apoptose, cancer et immunité ( U848 ), Université Paris-Sud - Paris 11 ( UP11 ) -Institut Gustave Roussy ( IGR ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Mount Sinai School of Medicine, Thomas Jefferson University-Kimmel Cancer Institute, University of Massachusetts Medical School [Worcester] ( UMASS ), Roswell Park Cancer Institute [Buffalo], Institute of Neuroscience and Physiology [Göteborg]-University of Gothenburg ( GU ), Institute of Molecular Medicine and Cell Research ( ZBMZ ), Albert-Ludwigs University, Laboratoire de génétique et biologie cellulaire ( LGBC ), Université de Versailles Saint-Quentin-en-Yvelines ( UVSQ ) -École pratique des hautes études ( EPHE ) -Centre National de la Recherche Scientifique ( CNRS ), National Institutes of Health ( NIH ), Università degli studi 'G. d'Annunzio' Chieti-Pescara [Chieti-Pescara] ( Ud'A ), Istituto Superiore di Sanita [Rome], The University of North Carolina at Chapel Hill, University of Pennsylvania School of Medicine, Yale School of Medicine, Howard Hughes Medical Institute, Howard Hugues Medical Institute, Lipides - Nutrition - Cancer (U866) ( LNC ), Université de Bourgogne ( UB ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Ecole Nationale Supérieure de Biologie Appliquée à la Nutrition et à l'Alimentation de Dijon ( ENSBANA ), Centre d'Immunologie de Marseille - Luminy ( CIML ), Aix Marseille Université ( AMU ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ), Institut Pasteur [Paris]-Institut National de la Santé et de la Recherche Médicale ( INSERM ), St. Jude Children's Research Hospital, Institut de Génétique et de Biologie Moléculaire et Cellulaire ( IGBMC ), Université de Strasbourg ( UNISTRA ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ), Johns Hopkins University ( JHU ), University of Zürich [Zürich] ( UZH ), The University of Tokyo, Weizmann Institute of Science, University College of London [London] ( UCL ), The Scripps Research Institute, University of California [San Diego] ( UC San Diego ), National Institutes of Health ( NIH ) -National Institute of Allergy and Infectious Diseases, University of Graz, Ghent University [Belgium] ( UGENT ), Academic Medical Center [Amsterdam] ( AMC ), University of Amsterdam [Amsterdam] ( UvA ) -University of Amsterdam [Amsterdam] ( UvA ), University of Amsterdam [Amsterdam] ( UvA ), Université Claude Bernard Lyon 1 ( UCBL ), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique ( CNRS ), Stony Brook University [The State University of New York] ( SBU ), University of Göttingen, Kyoto University [Kyoto]-Graduate School of Medicine, Merck and Co [Rahway], University of Michigan Medical School, Austrian Academy of Sciences ( OeAW ), National University of Singapore ( NUS ) -Yong Loo Lin School of Medicine-Graduate School for Integrative Sciences and Engineering, Singapore-MIT Alliance, National University of Singapore ( NUS ), Duke-NUS Graduate Medical School, Royal College of Surgeons in Ireland, Instituto de Biología y Medicina Experimental (IBYME- CONICET), Universita degli Studi di Padova = University of Padua = Université de Padoue, University of Lisbon, Cambridge Institute for Medical Research, University of Würzburg, Venetian Institute of Molecular Medicine, The Rockefeller University, Université de Lausanne ( UNIL ), Vib Ghent University, National Institutes of Health ( NIH ) -National Institute of Neurological Disorders and Stroke, Harvard Medical School [Boston] ( HMS ), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ), University of Pennsylvania [Philadelphia]-University of Pennsylvania [Philadelphia], Yale University School of Medicine, Institut Pasteur [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA), University of California, Karl-Franzens-Universität [Graz, Autriche], Universiteit Gent = Ghent University [Belgium] (UGENT), Georg-August-University [Göttingen], Universita degli Studi di Padova, Universidade de Lisboa (ULISBOA), Julius-Maximilians-Universität Würzburg [Wurtzbourg, Allemagne] (JMU), Université de Lausanne (UNIL), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-École pratique des hautes études (EPHE), Peney, Maité, Galluzzi, L, Aaronson, SA, Abrams, J, Alnemri, ES, Kumar, Sharad, and Kroemer, Guido
Subjects: MESH: Cell Death, cytofluorometry, MESH : Microscopy, Fluorescence, ved/biology.organism_classification_rank.species, Cell, MESH: Flow Cytometry, MESH: Microscopy, Fluorescence, Apoptosis, fluorescence microscopy, MESH: Eukaryotic Cells, Annexin V, necrosis, 0302 clinical medicine, Eukaryotic Cells/cytology, Mitochondrial membrane permeabilization, Scanning, MESH : Immunoblotting, Genetics, Cell Death, Flow Cytometry, Guidelines as Topic, Humans, Immunoblotting, Microscopy, Electron, Scanning, Microscopy, Fluorescence, Spectrometry, Fluorescence, 0303 health sciences, Microscopy, MESH : Spectrometry, Fluorescence, MESH: Immunoblotting, MESH: Guidelines as Topic, purl.org/becyt/ford/3.1 [https], Bioquímica y Biología Molecular, 3. Good health, Tunel, Medicina Básica, medicine.anatomical_structure, Eukaryotic Cells, caspases, 030220 oncology & carcinogenesis, purl.org/becyt/ford/3 [https], MESH: Spectrometry, Fluorescence, MESH : Microscopy, Electron, Scanning, Programmed cell death, autophagy, CIENCIAS MÉDICAS Y DE LA SALUD, MESH: Microscopy, Electron, Scanning, MESH : Flow Cytometry, caspase, Computational biology, Biology, Electron, Fluorescence, Article, 03 medical and health sciences, Settore MED/04 - PATOLOGIA GENERALE, medicine, [SDV.BBM] Life Sciences [q-bio]/Biochemistry, Molecular Biology, [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology, Model organism, ddc:612, mitotic catastrophe, Molecular Biology, [ SDV.BBM ] Life Sciences [q-bio]/Biochemistry, Molecular Biology, MESH : Guidelines as Topic, 030304 developmental biology, cell death, Oxidative stress, MESH: Humans, ved/biology, Spectrometry, Interpretation (philosophy), MESH: Apoptosis, MESH : Eukaryotic Cells, MESH : Humans, Cell Biology, immunofluorescence microscopy, MESH : Cell Death, Cancer cell, MESH : Apoptosis
Abstract: Cell death is essential for a plethora of physiological processes, and its deregulation characterizes numerous human diseases. Thus, the in-depth investigation of cell death and its mechanisms constitutes a formidable challenge for fundamental and applied biomedical research, and has tremendous implications for the development of novel therapeutic strategies. It is, therefore, of utmost importance to standardize the experimental procedures that identify dying and dead cells in cell cultures and/or in tissues, from model organisms and/or humans, in healthy and/or pathological scenarios. Thus far, dozens of methods have been proposed to quantify cell death-related parameters. However, no guidelines exist regarding their use and interpretation, and nobody has thoroughly annotated the experimental settings for which each of these techniques is most appropriate. Here, we provide a nonexhaustive comparison of methods to detect cell death with apoptotic or nonapoptotic morphologies, their advantages and pitfalls. These guidelines are intended for investigators who study cell death, as well as for reviewers who need to constructively critique scientific reports that deal with cellular demise. Given the difficulties in determining the exact number of cells that have passed the point-of-no-return of the signaling cascades leading to cell death, we emphasize the importance of performing multiple, methodologically unrelated assays to quantify dying and dead cells. Fil: Galluzzi, L.. Inserm; Francia. Universite Paris Sud; Francia. Institut Gustave Roussy; Francia Fil: Aaronson, S. A.. Mount Sinai School of Medicine; Estados Unidos Fil: Abrams, J.. University of Texas. Southwestern Medical Center; Estados Unidos Fil: Alnemri, E. S.. Thomas Jefferson University; Estados Unidos Fil: Andrews, D. W.. McMaster University; Canadá Fil: Baehrecke, E. H.. University of Massachussets; Estados Unidos Fil: Bazan, N. G.. Louisiana State University Health Sciences Center; Estados Unidos Fil: Blagosklonny, M. V.. Roswell Park Cancer Institute; Estados Unidos Fil: Blomgren, K.. Universityt of Gothenburg; Suecia. The Queen Silvia Children; Suecia Fil: Borner, C.. Albert-Ludwigs Universität Freiburg; Alemania Fil: Bredesen, E.. Buck Institute for Age Research; Estados Unidos. University of California; Estados Unidos Fil: Brenner, C.. univeristy of Versailles ; Francia Fil: Castedo, M.. Inserm; Francia. Universite Paris Sud; Francia Fil: Cidlowski, J. A.. National Institutes of Health; Estados Unidos Fil: Ciechanover, A.. The Rappaport Faculty of Medicine; Israel Fil: Cohen, G. M.. University of Leicester; Reino Unido Fil: De Laurenzi, V.. Università ‘G. d’Annunzio’ Chieti Pescara; Italia Fil: De Maria, R.. Istituto Superiore di Sanità; Italia. Mediterranean Institute of Oncology; Italia Fil: Deshmukh, M.. University of North Carolina; Estados Unidos Fil: Dynlacht, B. D.. University of New York; Estados Unidos Fil: El Deiry, W. S.. University of Pennsylvania; Estados Unidos Fil: Flavell, R. A.. University of Yale; Estados Unidos Fil: Fulda, S.. University Children; Alemania Fil: Garrido, C.. Inserm; Francia. University of Burgundy; Francia Fil: Golstein, P.. Inserm; Francia. Aix Marseille Université; Francia Fil: Gougeon, M. L.. Instituto Pasteur; Francia Fil: Green, D. R.. St. Jude Children′s Research Hospital; Estados Unidos Fil: Gronemeyer, H.. Institut de Génétique et de Biologie Moléculaire et Cellulaire; Francia. Inserm; Francia Fil: Hajnóczky, G.. Thomas Jefferson University; Estados Unidos Fil: Hardwick, J. M.. Johns Hopkins University; Estados Unidos Fil: Hengartner, M.O.. University Johns Hopkins; Estados Unidos Fil: Ichijo, H.. University of Tokyo; Japón Fil: Jäättelä, M.. Institute of Cancer Biology; Dinamarca Fil: Kepp, O.. Inserm; Francia. Universite Paris Sud; Francia. Institut Gustave Roussy; Francia Fil: Kimchi, A.. Weizmann Institute of Science; Israel Fil: Klionsky, D. J.. University of Michigan; Estados Unidos Fil: Knight, R. A.. University College London; Estados Unidos Fil: Kornbluth, S.. University of Duke; Estados Unidos Fil: Kumar, S.. Hanson Institute; Australia Fil: Levine, B.. Howard Hughes Medical Institute; Estados Unidos. University of Texas; Estados Unidos Fil: Lipton, S. A.. Burnham Institute for Medical Research; Estados Unidos. The Salk Institute for Biological Studies; Estados Unidos. The Scripps Research Institute; Estados Unidos. University of California at San Diego; Estados Unidos Fil: Lugli, E.. National Institutes of Health; Estados Unidos Fil: Madeo, F.. university of Graz; Austria Fil: Malorni, W.. Istituto Superiore di Sanità; Italia Fil: Marine, J. C.. VIB; Bélgica. Ghent University; Bélgica Fil: Martin, S. J.. Trinity College; Irlanda Fil: Medema, J. P.. Academic Medical Center; Países Bajos. University of Amsterdam; Países Bajos Fil: Mehlen, P.. Centre Léon Berard; Francia. Centre National de la Recherche Scientifique; Francia. Universite Lyon 2; Francia Fil: Melino, G.. University of Leicester; Reino Unido. Göttingen Center of Molecular Biosciences; Alemania Fil: Moll, U. M.. Stony Brook University; Estados Unidos. Göttingen Center of Molecular Biosciences; Alemania. University of Göttingen; Alemania Fil: Morselli, E.. Inserm; Francia. Universite Paris Sud; Francia. Institut Gustave Roussy; Francia Fil: Nagata, S.. University of Kyoto; Japón Fil: Nicholson, D. W.. Merck Research Laboratories; Estados Unidos Fil: Nicotera, P.. University of Leicester; Reino Unido Fil: Nuñez, G.. University of Michigan; Estados Unidos Fil: Oren, M.. Weizmann Institute of Science; Israel Fil: Penninger, J.. Institute of Molecular Biotechnology of the Austrian Academy of Science; Austria Fil: Pervaiz, S.. National University of Singapore; Singapur. Duke-NUS Graduate Medical School; Singapur Fil: Peter, M. E.. University of Chicago; Estados Unidos Fil: Piacentini, M.. National Institute for Infectious Diseases IRCCS "L. Spallanzani"; Italia. University of Rome "Tor Vergata"; Italia Fil: Prehn. J. H.. Royal College of Surgeons in Ireland; Irlanda Fil: Puthalakath, H.. La Trobe University; Australia Fil: Rabinovich, Gabriel Adrián. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; Argentina Fil: Rizzuto, R.. Università di Padova; Italia Fil: Rodrigues, C. M.. Universidade de Lisboa; Portugal Fil: Rubinsztein, D. C.. Cambridge Institute for Medical Research; Reino Unido Fil: Rudel, T.. University of Würzburg; Alemania Fil: Scorrano, L.. University of Geneva ; Suiza. Venetian Institute of Molecular Medicine; Italia Fil: Simon, H. U.. University of Bern; Suiza Fil: Steller, H.. Howard Hughes Medical Institute; Estados Unidos. The Rockefeller University; Estados Unidos Fil: Tschoop, J.. University of Lausanne; Suiza Fil: Tsujimoto, Y.. Osaka University Medical School; Japón Fil: Vandenabeele, P.. Ghent University; Bélgica. VIB; Bélgica Fil: Vitale, I.. Inserm; Francia. Universite Paris Sud; Francia. Institut Gustave Roussy; Francia Fil: Vousden, K. H.. The Beatson Institute for Cancer Research; Reino Unido Fil: Youle, J. R.. National Institutes of Health; Estados Unidos Fil: Yuan, J.. Harvard Medical School; Estados Unidos Fil: Zhivotovsky, B.. Karolinska Huddinge Hospital. Karolinska Institutet; Suecia Fil: Kroemer, G.. Inserm; Francia. Universite Paris Sud; Francia. Institut Gustave Roussy; Francia
Published: 2009
Full Text: View/download PDF

40. Comparative analysis of oncogenic properties and nuclear factor-kappaB activity of latent membrane protein 1 natural variants from Hodgkin's lymphoma's Reed-Sternberg cells and normal B-lymphocytes

Author: Fabienne Meggetto, Alan Bénard, Nadine Cogne, Aurélie Chanut, Nathalie Faumont, Georges Delsol, Jean Feuillard, Physiologie Moléculaire de la Réponse Immune et des Lymphoproliférations (PMRIL), Université de Limoges (UNILIM)-Génomique, Environnement, Immunité, Santé, Thérapeutique (GEIST FR CNRS 3503)-Centre National de la Recherche Scientifique (CNRS), Laboratoire d'Ecologie Microbienne - UMR 5557 (LEM), Centre National de la Recherche Scientifique (CNRS)-Ecole Nationale Vétérinaire de Lyon (ENVL)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Recherche Agronomique (INRA)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS), Centre de Physiopathologie Toulouse Purpan ex IFR 30 et IFR 150 (CPTP), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS), Institut National de la Recherche Agronomique (INRA)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Ecole Nationale Vétérinaire de Lyon (ENVL), Centre de Physiopathologie Toulouse Purpan (CPTP), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Physiologie Moléculaire de la Réponse Immune et des Lymphoproliférations ( PMRIL ), Université de Limoges ( UNILIM ) -Génomique, Environnement, Immunité, Santé, Thérapeutique ( GEIST FR CNRS 3503 ) -Centre National de la Recherche Scientifique ( CNRS ), Ecologie microbienne ( EM ), Centre National de la Recherche Scientifique ( CNRS ) -Ecole Nationale Vétérinaire de Lyon ( ENVL ) -Université Claude Bernard Lyon 1 ( UCBL ), Université de Lyon-Université de Lyon-Institut National de la Recherche Agronomique ( INRA ) -VetAgro Sup ( VAS ), Centre de Physiopathologie Toulouse Purpan, and Université Paul Sabatier - Toulouse 3 ( UPS ) -IFR30-IFR150-Institut National de la Santé et de la Recherche Médicale ( INSERM )
Subjects: MESH : Cell Line, MESH : Molecular Sequence Data, DNA Mutational Analysis, MESH: NF-kappa B, Apoptosis, MESH: Base Sequence, medicine.disease_cause, 0302 clinical medicine, MESH : Tumor Cells, Cultured, MESH: Luciferases, Renilla, immune system diseases, hemic and lymphatic diseases, MESH : Hodgkin Disease, Tumor Cells, Cultured, [ SDV.IMM ] Life Sciences [q-bio]/Immunology, MESH: Animals, MESH : Viral Matrix Proteins, MESH: Genetic Variation, Reed-Sternberg Cells, MESH: DNA Mutational Analysis, MESH : Immunoblotting, MESH: Reed-Sternberg Cells, Oncogene Proteins, Genetics, B-Lymphocytes, 0303 health sciences, Mutation, MESH: Immunoblotting, MESH : Oncogene Proteins, NF-kappa B, Hematology, Transfection, Hodgkin Disease, MESH: Hodgkin Disease, MESH : NF-kappa B, 030220 oncology & carcinogenesis, [SDV.IMM]Life Sciences [q-bio]/Immunology, MESH : Mutation, MESH : Transfection, MESH: Mutation, MESH : Recombinant Fusion Proteins, Recombinant Fusion Proteins, Immunoblotting, Molecular Sequence Data, MESH : Luciferases, Renilla, MESH : DNA Mutational Analysis, Biology, MESH: Sequence Homology, Nucleic Acid, MESH : B-Lymphocytes, Cell Line, Viral Matrix Proteins, 03 medical and health sciences, MESH: Oncogene Proteins, stomatognathic system, MESH : Genetic Variation, Sequence Homology, Nucleic Acid, MESH: B-Lymphocytes, medicine, otorhinolaryngologic diseases, MESH: Recombinant Fusion Proteins, Animals, Humans, Hodgkin's Lymphoma, MESH : Sequence Homology, Nucleic Acid, MESH: Tumor Cells, Cultured, Luciferases, Renilla, 030304 developmental biology, MESH: Viral Matrix Proteins, MESH: Molecular Sequence Data, MESH: Humans, MESH : Reed-Sternberg Cells, Base Sequence, MESH: Apoptosis, MESH: Transfection, MESH : Humans, Genetic Variation, medicine.disease, Hodgkin's lymphoma, Epstein–Barr virus, Lymphoma, MESH: Cell Line, stomatognathic diseases, Reed–Sternberg cell, Cell culture, Cancer research, MESH : Base Sequence, MESH : Animals, Carcinogenesis, MESH : Apoptosis
Abstract: International audience; BACKGROUND: In Epstein-Barr virus-associated Hodgkin's lymphomas, neoplastic Reed-Sternberg cells and surrounding non-tumor B-cells contain different variants of the LMP1-BNLF1 oncogene. In this study, we raised the question of functional properties of latent membrane protein 1 (LMP1) natural variants from both Reed-Sternberg and non-tumor B-cells. DESIGN AND METHODS: Twelve LMP1 natural variants from Reed-Sternberg cells, non-tumor B-cells of Hodgkin's lymphomas and from B-cells of benign reactive lymph nodes were cloned, sequenced and stably transfected in murine recombinant interleukin-3-dependent Ba/F3 cells to search for relationships between LMP1 cellular origin and oncogenic properties as well as nuclear factor-kappaB activation, and apoptosis protection. RESULTS: LMP1 variants of Reed-Sternberg cell origin were often associated with increased mutation rate and with recurrent genetic events, such as del15bp associated with S to N replacement at codon 309, and four substitutions I85L, F106Y, I122L, and M129I. Oncogenic potential (growth factor-independence plus clonogenicity) was consistently associated with LMP1 variants from Reed-Sternberg cells, but inconstantly for LMP1-variants from non-tumor B-cells. Analysis of LMP1 variants from both normal B-cells and Reed-Sternberg cells indicates that protection against apoptosis through activation of nuclear factor-kappaB - whatever the cellular origin of LMP1 - was maintained intact, regardless of the mutational pattern. CONCLUSIONS: Taken together, our results demonstrate that preserved nuclear factor-kappaB activity and protection against apoptosis would be the minimal prerequisites for all LMP1 natural variants from both normal and tumor cells in Hodgkin's lymphomas, and that oncogenic potential would constitute an additional feature for LMP1 natural variants in Reed-Sternberg cells.
Published: 2009
Full Text: View/download PDF

41. Cancer stem cells from human glioma cell line are resistant to Fas-induced apoptosis

Author: Barbara Bessette, Gaëlle Begaud-Grimaud, Serge Battu, Marie-Odile Jauberteau, Mireille Verdier, Julian Bertrand, Homéostasie Cellulaire et Pathologies (HCP), Université de Limoges (UNILIM)-CHU Limoges-Génomique, Environnement, Immunité, Santé, Thérapeutique (GEIST FR CNRS 3503), Laboratoire de Chimie des Substances Naturelles (LCSN), Université de Limoges (UNILIM)-Génomique, Environnement, Immunité, Santé, Thérapeutique (GEIST FR CNRS 3503), Service de Médecine interne A et polyclinique médicale [CHU Limoges], CHU Limoges, Homéostasie Cellulaire et Pathologies ( HCP ), Université de Limoges ( UNILIM ) -Génomique, Environnement, Immunité, Santé, Thérapeutique ( GEIST FR CNRS 3503 ) -CHU Limoges, Laboratoire de Chimie des Substances Naturelles ( LCSN ), and Université de Limoges ( UNILIM ) -Génomique, Environnement, Immunité, Santé, Thérapeutique ( GEIST FR CNRS 3503 )
Subjects: Cancer Research, Cellular differentiation, [SDV.NEU.NB]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Neurobiology, Apoptosis, MESH: Flow Cytometry, [ SDV.CAN ] Life Sciences [q-bio]/Cancer, MESH: Antibodies, Monoclonal, 0302 clinical medicine, AC133 Antigen, MESH: Antigens, CD, 0303 health sciences, MESH : Cell Survival, Brain Neoplasms, MESH : Peptides, MESH: Peptides, MESH: Glioblastoma, Antibodies, Monoclonal, Flow Cytometry, Fas receptor, Neural stem cell, 3. Good health, Cell biology, MESH: Antigens, CD95, Endothelial stem cell, Oncology, MESH: Cell Survival, 030220 oncology & carcinogenesis, MESH : Antibodies, Monoclonal, [ SDV.NEU.NB ] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Neurobiology, MESH: Brain Neoplasms, Neoplastic Stem Cells, Stem cell, MESH: Cell Line, Tumor, Cell Survival, MESH : Flow Cytometry, MESH: Glycoproteins, [SDV.CAN]Life Sciences [q-bio]/Cancer, [SDV.BC]Life Sciences [q-bio]/Cellular Biology, Biology, MESH : Glioblastoma, 03 medical and health sciences, MESH : Neoplastic Stem Cells, Antigens, CD, Cancer stem cell, Cell Line, Tumor, Neurosphere, MESH : Antigens, CD, Humans, fas Receptor, MESH : Brain Neoplasms, Glycoproteins, 030304 developmental biology, MESH: Humans, MESH : Cell Line, Tumor, [ SDV.BC ] Life Sciences [q-bio]/Cellular Biology, MESH: Apoptosis, MESH : Humans, MESH : Glycoproteins, MESH: Neoplastic Stem Cells, Immunology, MESH : Antigens, CD95, Glioblastoma, Peptides, MESH : Apoptosis
Abstract: International audience; Glioblastoma is the most common primary brain tumor, characterized by its resistance to treatments. To define efficient therapy, the origin of tumor-forming cells needs to be elucidated in order to search for new therapeutic pathways. The objective of this study was to determine the different cell populations constituting a human glioblastoma cell line, U-87 MG and their sensitivity to apoptosis induced through the activation of Fas, a membranous death receptor. By a cell sorting method, the sedimentation field flow fractionation, two major cell subpopulations were identified, a most differentiated cell fraction, containing large and adherent cells, sensitive to Fas-induced apoptosis and another one, characterized by small cells forming aggregates, expressing CD133, a marker of stem cells and more resistant to Fas-activated apoptosis. By using a selective method of culture, adapted for neural stem cell cultures, we have verified that the U-87 MG cell line contained cancer stem cells similar to the immature ones obtained by the cell sorting method. Interestingly, while these tumor stem cells, expressing CD133, were resistant to Fas-induced apoptosis, monomeric form of Fas protein was detected predominantly in these cells. In contrast, the most mature cells, responsive to Fas-activated apoptosis, collected in another cell fraction, contained oligomeric aggregates of Fas protein, a pre-signalling form of the Fas receptor, essential for the initiation of apoptosis through its activation. These results suggest that these immature stem cells in glioma could be an important factor of resistance to chemotherapy requiring apoptosis through Fas signalling system. Indeed, future strategies of treatment, inducing differentiation of these stem cells need to be considered to enhance therapeutic efficiency.
Published: 2009
Full Text: View/download PDF

42. Autophagy: a novel mechanism of synergistic cytotoxicity between doxorubicin and roscovitine in a sarcoma model

Author: Laurent Meijer, Gordon B. Mills, Khandan Keyomarsi, Donald H. Lambert, Laura A. Lambert, Na Qiao, Kelly K. Hunt, Biogéosciences [UMR 6282] (BGS), Université de Bourgogne (UB)-Centre National de la Recherche Scientifique (CNRS), Program in integrative biology. Research Institute, The Hospital for sick children [Toronto] (SickKids), Unité de Chimie Pharmaceutique et Radiopharmacie (UCL-CMFA 7340), Université Catholique de Louvain = Catholic University of Louvain (UCL), School of Environmental Sciences [Norwich], University of East Anglia [Norwich] (UEA), Molécules et cibles thérapeutiques (MCT), Station biologique de Roscoff [Roscoff] (SBR), Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS), Biogéosciences [UMR 6282] [Dijon] (BGS), Centre National de la Recherche Scientifique (CNRS)-Université de Bourgogne (UB)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement, Biogéosciences [Dijon] ( BGS ), AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Université de Bourgogne ( UB ) -Centre National de la Recherche Scientifique ( CNRS ), The Hospital for Sick Children, Unité de Chimie Pharmaceutique et Radiopharmacie ( UCL-CMFA 7340 ), Université Catholique de Louvain ( UCL ), University of East Anglia [Norwich] ( UEA ), Molécules et cibles thérapeutiques ( MCT ), and Centre National de la Recherche Scientifique ( CNRS )
Subjects: Cancer Research, Cell cycle checkpoint, MESH : Antineoplastic Combined Chemotherapy Protocols, medicine.medical_treatment, Apoptosis, MESH : Models, Biological, Pharmacology, MESH: Drug Synergism, 0302 clinical medicine, MESH : Tumor Cells, Cultured, MESH : Cytotoxins, Antineoplastic Combined Chemotherapy Protocols, Tumor Cells, Cultured, MESH : G2 Phase, MESH : Purines, Cytotoxicity, Tumor Stem Cell Assay, 0303 health sciences, Cytotoxins, MESH: Tumor Stem Cell Assay, Drug Synergism, Sarcoma, MESH: Purines, Cell cycle, 3. Good health, MESH: Antineoplastic Combined Chemotherapy Protocols, Oncology, 030220 oncology & carcinogenesis, MESH: Cytotoxins, medicine.drug, G2 Phase, MESH : Drug Synergism, MESH : Tumor Stem Cell Assay, [SDV.BC]Life Sciences [q-bio]/Cellular Biology, Biology, MESH : Sarcoma, Models, Biological, Article, 03 medical and health sciences, MESH: Doxorubicin, Therapeutic index, medicine, Autophagy, Roscovitine, MESH : Doxorubicin, MESH: Autophagy, Humans, Doxorubicin, MESH: Tumor Cells, Cultured, 030304 developmental biology, Chemotherapy, MESH: Humans, [ SDV.BC ] Life Sciences [q-bio]/Cellular Biology, MESH: Apoptosis, MESH : Humans, MESH: Models, Biological, MESH : Autophagy, MESH: G2 Phase, Purines, MESH: Sarcoma, MESH : Apoptosis
Abstract: Doxorubicin is a genotoxic chemotherapy agent used in treatment of a wide variety of cancers. Significant clinical side effects, including cardiac toxicity and myelosuppression, severely limit the therapeutic index of this commonly used agent and methods which improve doxorubicin efficacy could benefit many patients. Because doxorubicin cytotoxicity is cell cycle specific, the cell cycle is a rational target to enhance its efficacy. We examined the direct, cyclin-dependent kinase inhibitor roscovitine as a means of enhancing doxorubicin cytotoxicity. This study showed synergistic cytotoxicity between doxorubicin and roscovitine in three sarcoma cell lines: SW-982 (synovial sarcoma), U2OS-LC3-GFP (osteosarcoma), and SK-LMS-1 (uterine leiomyosarcoma), but not the fibroblast cell line WI38. The combined treatment of doxorubicin and roscovitine was associated with a prolonged G2-M cell cycle arrest in the three sarcoma cell lines. Using three different methods for detecting apoptosis, our results revealed that apoptotic cell death did not account for the synergistic cytotoxicity between doxorubicin and roscovitine. However, morphologic changes observed by light microscopy and increased cytoplasmic LC3-GFP puncta in U20S-LC3-GFP cells after the combined treatment suggested the induction of autophagy. Induction of autophagy was also shown in SW-982 and SK-LMS-1 cells treated with both doxorubicin and roscovitine by acridine orange staining. These results suggest a novel role of autophagy in the enhanced cytotoxicity by cell cycle inhibition after genotoxic injury in tumor cells. Further investigation of this enhanced cytotoxicity as a treatment strategy for sarcomas is warranted. [Cancer Res 2008;68(19):7966–74]
Published: 2008
Full Text: View/download PDF

43. Differential expression of parathyroid hormone-related protein in adrenocortical tumors: autocrine/paracrine effects on the growth and signaling pathways in H295R cells

Author: Fernande René-Corail, Karine Perlemoine, Marthe Rizk-Rabin, Xavier Bertagna, Frédérique Tissier, Jérôme Bertherat, Michèle Lieberherr, Guillaume Assié, Z. Bouizar, Hinda Hamzaoui, Institut Cochin (UMR_S567 / UMR 8104), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Descartes - Paris 5 (UPD5), Pôle Endocrinologie-Diabétologie Adultes-Enfants, Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Cochin [AP-HP]-Hôpital Saint-Vincent de Paul, Nutrition et Régulation Lipidique des Fonctions Cérébrales, Institut National de la Recherche Agronomique (INRA), Service de biochimie-hormonologie [Béclère], Université Paris-Sud - Paris 11 (UP11)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpital Antoine Béclère, This study was supported in part by Plan Hospitalier de Recherche Clinique (PHRC) grant (AOM 06 179 to the Comete Network coordinated by Prof. P.F. Plouin) and by grants from INSERM and the Ministère Délégué à la Recherche et des Nouvelles Technologies. H. Hamzaoui was the recipient of fellowships from the Cancer & Solidarity Foundation, the Association pour la Recherche contre le Cancer (ARC) and the Fondation pour la Recherche Médicale (FRM)., Université Paris Descartes - Paris 5 (UPD5) - Institut National de la Santé et de la Recherche Médicale (INSERM) - Centre National de la Recherche Scientifique (CNRS), Assistance publique - Hôpitaux de Paris (AP-HP) - CHU Cochin [AP-HP] - Hôpital Saint-Vincent de Paul, Université Paris-Sud - Paris 11 (UP11) - Assistance publique - Hôpitaux de Paris (AP-HP) - Hôpital Antoine Béclère, Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Saint-Vincent de Paul, AP-HP - Hôpital Antoine Béclère [Clamart], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris-Sud - Paris 11 (UP11), Bouizar, Zhor, Université Paris-Sud - Paris 11 (UP11)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-AP-HP - Hôpital Antoine Béclère [Clamart], and Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)
Subjects: Male, MESH: Signal Transduction, MESH : RNA, Messenger, Epidemiology, MESH : Aged, MESH : Adrenal Cortex Neoplasms, Apoptosis, MESH: Cell Cycle, MESH : Blotting, Western, MESH: Adrenal Cortex Neoplasms, Metastasis, 0302 clinical medicine, MESH: Reverse Transcriptase Polymerase Chain Reaction, MESH : Female, Receptor, MESH: Aged, 0303 health sciences, MESH : Prognosis, MESH: Middle Aged, Reverse Transcriptase Polymerase Chain Reaction, Paracrine cAMP, Cell Cycle, MESH : Reverse Transcriptase Polymerase Chain Reaction, Middle Aged, MESH : Adult, Prognosis, musculoskeletal system, 3. Good health, Blot, MESH : Cyclic AMP-Dependent Protein Kinases, qPCR, Oncology, 030220 oncology & carcinogenesis, MESH: Calcium, Female, Signal transduction, PTHrP Receptor, MESH : Parathyroid Hormone-Related Protein, hormones, hormone substitutes, and hormone antagonists, Signal Transduction, Adult, musculoskeletal diseases, medicine.medical_specialty, MESH: Cell Line, Tumor, Adolescent, MESH : Male, PTHrP, Blotting, Western, Ca++ signaling Pathways, [SDV.CAN]Life Sciences [q-bio]/Cancer, MESH: Cyclic AMP-Dependent Protein Kinases, Biology, MESH: Parathyroid Hormone-Related Protein, MESH: Prognosis, Adrenocortical Tumors, 03 medical and health sciences, Paracrine signalling, MESH : Receptor, Parathyroid Hormone, Type 1, [SDV.CAN] Life Sciences [q-bio]/Cancer, Internal medicine, Cell Line, Tumor, MESH : Adolescent, MESH : Cell Cycle, medicine, Didderential Expression, Humans, MESH: Blotting, Western, MESH : Middle Aged, RNA, Messenger, Autocrine, Autocrine signalling, Protein kinase A, MESH : Calcium, Protein kinase C, 030304 developmental biology, Aged, Receptor, Parathyroid Hormone, Type 1, MESH: RNA, Messenger, MESH : Signal Transduction, MESH: Adolescent, MESH: Humans, Parathyroid hormone-related protein, MESH : Cell Line, Tumor, MESH: Apoptosis, MESH : Humans, Parathyroid Hormone-Related Protein, Antagonist, MESH: Adult, Cyclic AMP-Dependent Protein Kinases, Adrenal Cortex Neoplasms, MESH: Male, Endocrinology, MESH: Receptor, Parathyroid Hormone, Type 1, Cancer research, Calcium, MESH: Female, MESH : Apoptosis
Abstract: Adrenocortical tumors (ACT) are rare and heterogeneous, but their pathogenesis is unclear. The oncoprotein parathyroid hormone–related protein (PTHrP), found in many common tumors, can regulate their growth in an autocrine/paracrine fashion through the PTH-R1 receptor. Little is known about the role of PTHrP in ACT. We monitored the synthesis of PTHrP and PTH-R1 in a series of 25 ACT: 12 adrenocortical carcinomas (ACC) and 13 adrenocortical adenomas (ACA), and investigated the effects of PTHrP(1-34) on H295R cells derived from an ACC. PTH-R1 mRNA and proteins were detected by real-time PCR and Western blotting in all the ACT samples and in H295R cells. Their concentrations did not differ significantly from one ACT to another. PTHrP mRNA was assayed by quantitative real-time PCR. It was detected in 90% of ACC, and in 10% of ACA. There was a positive correlation with the prognostic factors, McFarlane stage and Weiss score. Tissue-specific PTHrP protein processing was shown by Western blotting. Immunohistochemical staining revealed numerous, dense foci of PTHrP-containing cells in ACC, but few positive cells in ACA or normal tissue. PTHrP stimulated the growth of H295R cells, whereas a specific anti-PTHrP antibody and a PTHrP-R1 antagonist both enhanced their apoptosis. PTHrP activated both adenylate cyclase/protein kinase A and the intracellular calcium/protein kinase C pathways via PTHrP-R1. The active synthesis of PTHrP is linked to poor prognosis in ACC, in which it may act as an autocrine/paracrine factor in tumor growth and malignancy. (Cancer Epidemiol Biomarkers Prev 2008;17(9):2275–85)
Published: 2008
Full Text: View/download PDF

44. Metabolic syndrome features small, apolipoprotein A-I-poor, triglyceride-rich HDL3 particles with defective anti-apoptotic activity

Author: Juliana A. de Souza, Carlos V. Serrano, Anatol Kontush, M. John Chapman, Anne Nègre-Salvayre, S. Chantepie, Cécile Vindis, Robert Salvayre, Boris Hansel, P. Thérond, Eric Bruckert, Heart Institute, Universidade de São Paulo = University of São Paulo (USP), Dyslipoproteinémies et athérosclerose : Génétique, métabolisme et thérapeutique, Université Pierre et Marie Curie - Paris 6 (UPMC)-IFR14-Institut National de la Santé et de la Recherche Médicale (INSERM), Régulations cellulaires: lipidoses et atherosclerose, IFR 31 Louis Bugnard (IFR 31), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM), Laboratoire de biochimie, Université Paris Descartes - Paris 5 (UPD5), CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Simon, Marie Francoise, Université de Toulouse (UT)-Université de Toulouse (UT)-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université de Toulouse (UT)-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM), University of São Paulo (USP), Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Toulouse [Toulouse]-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Toulouse [Toulouse]-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM), Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), University of São Paulo ( USP ), Université Pierre et Marie Curie - Paris 6 ( UPMC ) -IFR14-Institut National de la Santé et de la Recherche Médicale ( INSERM ), Régulations cellulaires: lipidoses et atherosclerose., IFR 31 Louis Bugnard ( IFR 31 ), Université Toulouse III - Paul Sabatier ( UPS ), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-CHU Toulouse [Toulouse]-Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ) -Université Toulouse III - Paul Sabatier ( UPS ), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-CHU Toulouse [Toulouse]-Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Université Paris Descartes - Paris 5 ( UPD5 ), and CHU Pitié-Salpêtrière [APHP]
Subjects: Male, MESH: Lipoproteins, LDL, Apolipoprotein B, medicine.medical_treatment, MESH: Apolipoprotein A-I, MESH : Reactive Oxygen Species, Apoptosis, 030204 cardiovascular system & hematology, medicine.disease_cause, chemistry.chemical_compound, 0302 clinical medicine, MESH: Metabolic Syndrome X, MESH : Particle Size, MESH: Endothelial Cells, Metabolic Syndrome, 0303 health sciences, MESH: Middle Aged, MESH: Reactive Oxygen Species, Middle Aged, MESH : Triglycerides, Lipoproteins, LDL, MESH: Insulin Resistance, MESH : Cholesterol, HDL, Cholesteryl ester, lipids (amino acids, peptides, and proteins), MESH : Apolipoprotein A-I, MESH: Cholesterol, HDL, MESH : Insulin Resistance, MESH : Lipoproteins, LDL, Cardiology and Cardiovascular Medicine, MESH: Triglycerides, medicine.medical_specialty, MESH : Male, MESH : Metabolic Syndrome X, Biology, 03 medical and health sciences, Insulin resistance, Internal medicine, medicine, Humans, MESH : Middle Aged, MESH: Particle Size, Particle Size, Triglycerides, 030304 developmental biology, MESH: Humans, Apolipoprotein A-I, MESH : Endothelial Cells, Insulin, MESH: Apoptosis, MESH : Humans, Cholesterol, HDL, Hypertriglyceridemia, Endothelial Cells, medicine.disease, MESH: Male, Endocrinology, chemistry, biology.protein, Insulin Resistance, Metabolic syndrome, Reactive Oxygen Species, MESH : Apoptosis, Oxidative stress, Lipoprotein
Abstract: International audience; The metabolic syndrome (MetS) phenotype is typically characterized by visceral obesity, insulin resistance, atherogenic dyslipidemia involving hypertriglyceridemia and subnormal levels of high density lipoprotein-cholesterol (HDL-C), oxidative stress and elevated cardiovascular risk. The potent antioxidative activity of small HDL3 is defective in MetS [Hansel B, et al. J Clin Endocrinol Metab 2004;89:4963-71]. We evaluated the functional capacity of small HDL3 particles from MetS subjects to protect endothelial cells from apoptosis induced by mildly oxidized low-density lipoprotein (oxLDL). MetS subjects presented an insulin-resistant obese phenotype, with hypertriglyceridemia, elevated apolipoprotein B and insulin levels, but subnormal HDL-C concentrations and chronic low grade inflammation (threefold elevation of C-reactive protein). When human microvascular endothelial cells (HMEC-1) were incubated with oxLDL (200 microg apolipoprotein B/ml) in the presence or absence of control HDL subfractions (25 microg protein/ml), small, dense HDL3b and 3c significantly inhibited cellular annexin V binding and intracellular generation of reactive oxygen species. The potent anti-apoptotic activity of small HDL3c particles was reduced (-35%; p
Published: 2008
Full Text: View/download PDF

45. Transforming growth factor beta controls the directional migration of hepatocyte cohorts by modulating their adhesion to fibronectin

Author: Urszula Hibner, Fabien Binamé, Patrice Lassus, Institut de Génétique Moléculaire de Montpellier ( IGMM ), Université de Montpellier ( UM ) -Centre National de la Recherche Scientifique ( CNRS ), Institut de Génétique Moléculaire de Montpellier (IGMM), and Centre National de la Recherche Scientifique (CNRS)-Université de Montpellier (UM)
Subjects: rac1 GTP-Binding Protein, MESH : Cell Line, MESH : Protein Subunits, Apoptosis, Cell Communication, Integrin alpha5, MESH : Hepatocytes, Epithelium, Mesoderm, MESH: Hepatocytes, Mice, 0302 clinical medicine, Cell Movement, Transforming Growth Factor beta, MESH: Fibronectins, MESH : Cell Movement, MESH : Fibronectins, MESH: Animals, MESH: Cell Movement, MESH: Mesoderm, 0303 health sciences, MESH : Gene Expression Regulation, MESH: Cell Surface Extensions, MESH : Mesoderm, Articles, Adhesion, MESH: Protein Subunits, MESH: Gene Expression Regulation, Cell biology, medicine.anatomical_structure, 030220 oncology & carcinogenesis, Hepatocyte, MESH: Integrin alpha5, MESH : Cell Communication, MESH : Cell Membrane, MESH : Cell Surface Extensions, Biology, Cell Line, MESH: Cell Adhesion, MESH: Gene Expression Profiling, 03 medical and health sciences, MESH : rac1 GTP-Binding Protein, MESH : Integrin alpha5, MESH: Cell Communication, MESH : Mice, Cell Adhesion, medicine, Animals, Humans, [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology, MESH: Mice, Molecular Biology, [ SDV.BBM ] Life Sciences [q-bio]/Biochemistry, Molecular Biology, MESH: Transforming Growth Factor beta, 030304 developmental biology, MESH: Humans, MESH: rac1 GTP-Binding Protein, Gene Expression Profiling, MESH: Apoptosis, MESH : Gene Expression Profiling, Cell Membrane, MESH : Humans, Cell Biology, MESH : Epithelium, Fibronectins, MESH: Cell Line, Fibronectin, Protein Subunits, MESH: Epithelium, MESH : Cell Adhesion, MESH : Transforming Growth Factor beta, Gene Expression Regulation, Hepatocytes, biology.protein, Cell Surface Extensions, MESH : Animals, MESH : Apoptosis, MESH: Cell Membrane, Transforming growth factor
Abstract: International audience; Transforming growth factor beta (TGF-beta) has a strong impact on liver development and physiopathology, exercised through its pleiotropic effects on growth, differentiation, survival, and migration. When exposed to TGF-beta, the mhAT3F cells, immortalized, highly differentiated hepatocytes, maintained their epithelial morphology and underwent dramatic alterations of adhesion, leading to partial or complete detachment from a culture plate, followed by readhesion and spreading. These alterations of adhesive behavior were caused by sequential changes in expression of the alpha5beta1 integrin and of its ligand, the fibronectin. The altered specificity of anchorage to the extracellular matrix gave rise to changes in cells' collective motility: cohorts adhering to fibronectin maintained a persistent, directional motility, with ezrin-rich pathfinder cells protruding from the tips of the cohorts. The absence of adhesion to fibronectin prevented the appearance of polarized pathfinders and lead to random, oscillatory motility. Our data suggest a novel role for TGF-beta in the control of collective migration of epithelial cohorts.
Published: 2008
Full Text: View/download PDF

46. ADRB3 adrenergic receptor is a key regulator of human myometrial apoptosis and inflammation during chorioamnionitis

Author: Lirussi, Fréderic, Rakotoniaina, Zo, Madani, Siham, Goirand, Françoise, Breuiller-Fouché, Michelle, Leroy, Marie-Josèphe, Sagot, Paul, Morrison, John, Dumas, Monique, Bardou, Marc, Laboratoire de Pharmacologie et Toxicologie, Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), La grossesse normale et pathologique: développement et fonctions du placenta et de l'utérus (UMR_S 767), Institut des sciences du Médicament -Toxicologie - Chimie - Environnement (IFR71), Institut National de la Santé et de la Recherche Médicale (INSERM)-Ecole Nationale Supérieure de Chimie de Paris - Chimie ParisTech-PSL (ENSCP), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Ecole Nationale Supérieure de Chimie de Paris - Chimie ParisTech-PSL (ENSCP), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD)-Université Paris Descartes - Paris 5 (UPD5)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Departments of Gynaecology and Obstetrics, Clinical Science Institute-National University of Ireland [Galway] (NUI Galway), Hôpital du Bocage, Centre d'Investigation Clinique 1432 (Dijon) - Module Plurithématique : Périnatalité Cancérologie Handicap et Ophtalmologie (CIC-P803), Université de Bourgogne (UB)-Direction Générale de l'Organisation des Soins (DGOS)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand ( CHU Dijon ), La grossesse normale et pathologique: développement et fonctions du placenta et de l'utérus ( UMR_S 767 ), Institut des sciences du Médicament -Toxicologie - Chimie - Environnement ( IFR71 ), Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Ecole Nationale Supérieure de Chimie de Paris- Chimie ParisTech-PSL ( ENSCP ) -Centre National de la Recherche Scientifique ( CNRS ) -Institut de Recherche pour le Développement ( IRD ) -Université Paris Descartes - Paris 5 ( UPD5 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Ecole Nationale Supérieure de Chimie de Paris- Chimie ParisTech-PSL ( ENSCP ) -Centre National de la Recherche Scientifique ( CNRS ) -Institut de Recherche pour le Développement ( IRD ) -Université Paris Descartes - Paris 5 ( UPD5 ) -Université Paris Descartes - Paris 5 ( UPD5 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Clinical Science Institute-National University of Ireland [Galway] ( NUI Galway ), Unité de Pharmacologie Clinique, Laboratoire de Physiopathologie et de Pharmacologie Cardiovasculaire Expérimentale (LPPCE), Université de Bourgogne (UB), Institut de Recherche pour le Développement (IRD)-Ecole Nationale Supérieure de Chimie de Paris - Chimie ParisTech-PSL (ENSCP), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD)-Ecole Nationale Supérieure de Chimie de Paris - Chimie ParisTech-PSL (ENSCP), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service de Gynécologie Obstétrique, Médecine Foetale et Stérilité Conjugale - Chirurgie Gynécologie et Oncologique [CHU de Dijon], and Breuiller-Fouche, Michelle
Subjects: Lipopolysaccharides, MESH : Benzoates, MESH: Inflammation, Pregnancy Trimester, Third, MESH : Cytokines, MESH : Receptors, Adrenergic, beta-3, MESH: Sulfonamides, Adrenergic beta-3 Receptor Agonists, Apoptosis, MESH : Pregnancy Trimester, Third, [SDV.BC]Life Sciences [q-bio]/Cellular Biology, MESH : Lipopolysaccharides, Benzoates, MESH : Chorioamnionitis, MESH: Pregnancy, Pregnancy, Humans, MESH : Female, [SDV.BC] Life Sciences [q-bio]/Cellular Biology, MESH : Sulfonamides, Inflammation, Sulfonamides, MESH: Cytokines, MESH : Inflammation, MESH: Humans, [ SDV.BC ] Life Sciences [q-bio]/Cellular Biology, MESH : Myometrium, MESH: Apoptosis, MESH: Chorioamnionitis, MESH : Humans, MESH: Benzoates, MESH : Pregnancy, Chorioamnionitis, Receptors, Adrenergic, beta-3, Myometrium, MESH: Pregnancy Trimester, Third, Cytokines, MESH: Myometrium, Female, MESH: Lipopolysaccharides, MESH: Receptors, Adrenergic, beta-3, MESH: Female, MESH : Apoptosis
Abstract: International audience; The pathophysiology underlying preterm labor triggered by inflammatory conditions such as chorioamnionitis remains largely unclear. It has already been suggested that beta-3 adrenergic (ADRB3) agonists might be of interest in the pharmacological management of preterm labor. Although there is evidence implicating ADRB receptors in the control of inflammation, there are minimal data relating specifically to ADRB3. To explore the cellular consequences of chorioamnionitis and detect apoptosis, we first performed immunostaining and Western blot experiments on human myometrial samples obtained from women with confirmed chorioamnionitis. We then developed an in vitro model of chorioamnionitis by incubating the myometrial samples obtained from uncomplicated pregnancies with Escherichia coli lipopolysaccharide (LPS). We observed that chorioamnionitis was associated with a significant increase in cleaved CASP3 protein expression, as well as chromatin condensation, which were reproduced experimentally by LPS stimulation (10 microg/ml, 48 h). Lipopolysaccharide stimulation of normal human myometrium also induced CASP3 transcripts, increased the proapoptotic marker BAX, and decreased the antiapoptotic marker BCL2. Lipopolysaccharide-induced apoptosis was antagonized by neutralization of secreted tumor necrosis factor by a specific antibody. Furthermore, LPS stimulation increased medium culture levels of proinflammatory cytokines interleukin 6 (IL6) and IL8. Lipopolysaccharide-induced apoptosis and cytokine production were prevented by the new and potent ADRB3 agonist SAR150640 in a concentration-dependent manner. SAR150640 by itself did not exhibit any effect on apoptosis or cytokine production in control tissues. This study shows that chorioamnionitis is associated with apoptosis of human myometrial cells. It emphasizes the potential therapeutic interest of ADRB3 agonists in the field of preterm labor and other inflammatory conditions.
Published: 2008
Full Text: View/download PDF

47. Meriolins (3-(pyrimidin-4-yl)-7-azaindoles): synthesis, kinase inhibitory activity, cellular effects, and structure of a CDK2/cyclin A/meriolin complex

Author: Olivier Lozach, Annie Valette, Laurent Meijer, Monique Clément, François Liger, Aude Echalier, Yoan Ferandin, Karima Bettayeb, Jonathan C. Morris, Bernard Marquet, Jane A. Endicott, Benoît Joseph, Molécules et cibles thérapeutiques (MCT), Station biologique de Roscoff [Roscoff] (SBR), Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS), Laboratoire de Biologie Cellulaire et Moléculaire du Contrôle de la Prolifération (LBCMCP), Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre de Biologie Intégrative (CBI), Université de Toulouse (UT)-Université de Toulouse (UT)-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS), Centre d'études et de recherches appliquées à la gestion (CERAG), Université Pierre Mendès France - Grenoble 2 (UPMF)-Centre National de la Recherche Scientifique (CNRS), Institut de Mathématiques (UNINE), Université de Neuchâtel (UNINE), Centre de recherche en gestion (CRG), École polytechnique (X)-Centre National de la Recherche Scientifique (CNRS), Institut de Chimie et Biochimie Moléculaires et Supramoléculaires (ICBMS), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-École Supérieure de Chimie Physique Électronique de Lyon (CPE)-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre de Biologie Intégrative (CBI), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS), Centre National de la Recherche Scientifique (CNRS)-Université Pierre Mendès France - Grenoble 2 (UPMF), Centre National de la Recherche Scientifique (CNRS)-École polytechnique (X), Université de Lyon-Université de Lyon-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Institut National des Sciences Appliquées (INSA)-Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut de Chimie du CNRS (INC)-École Supérieure Chimie Physique Électronique de Lyon-Centre National de la Recherche Scientifique (CNRS), Molécules et cibles thérapeutiques ( MCT ), Centre National de la Recherche Scientifique ( CNRS ), Laboratoire d'économie et de sociologie du travail ( LEST ), Aix Marseille Université ( AMU ) -Centre National de la Recherche Scientifique ( CNRS ), Biologie cellulaire et moléculaire du contrôle de la prolifération ( BCMCP ), Université Paul Sabatier - Toulouse 3 ( UPS ) -Centre National de la Recherche Scientifique ( CNRS ), Centre d'études et de recherches appliquées à la gestion ( CERAG ), Université Pierre Mendès France - Grenoble 2 ( UPMF ) -Centre National de la Recherche Scientifique ( CNRS ), Institut de Mathématiques ( UNINE ), Université de Neuchâtel, Centre de recherche en gestion ( CRG ), École polytechnique ( X ) -Centre National de la Recherche Scientifique ( CNRS ), Institut de Chimie et Biochimie Moléculaires et Supramoléculaires ( ICBMS ), Université Claude Bernard Lyon 1 ( UCBL ), Université de Lyon-Université de Lyon-Institut National des Sciences Appliquées de Lyon ( INSA Lyon ), Université de Lyon-Institut National des Sciences Appliquées ( INSA ) -Institut National des Sciences Appliquées ( INSA ) -École Supérieure Chimie Physique Électronique de Lyon-Centre National de la Recherche Scientifique ( CNRS ), Laboratoire d'économie et de sociologie du travail (LEST), Aix Marseille Université (AMU)-Centre National de la Recherche Scientifique (CNRS), and Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Institut de Chimie du CNRS (INC)-École Supérieure Chimie Physique Électronique de Lyon-Centre National de la Recherche Scientifique (CNRS)
Subjects: Models, Molecular, MESH : Cell Line, Indoles, DYRK1A, Cyclin A, MESH : Pyrimidines, MESH: Spheroids, Cellular, Apoptosis, Crystallography, X-Ray, 01 natural sciences, MESH: Bicyclo Compounds, Heterocyclic, MESH : Bicyclo Compounds, Heterocyclic, MESH: Structure-Activity Relationship, MESH : Indoles, Drug Discovery, MESH : Structure-Activity Relationship, MESH : Cyclin A, MESH: Crystallization, MESH: Indoles, 0303 health sciences, MESH : Cell Survival, biology, Chemistry, Kinase, MESH : Drug Screening Assays, Antitumor, MESH: Drug Screening Assays, Antitumor, MESH : Cyclin-Dependent Kinase 2, 3. Good health, MESH : Antineoplastic Agents, MESH : Cyclin-Dependent Kinase 9, Biochemistry, MESH: Cell Survival, MESH : Crystallization, Molecular Medicine, Crystallization, MESH: Models, Molecular, MESH: Cell Line, Tumor, Cell Survival, MESH : Models, Molecular, MESH: Cyclin-Dependent Kinase 2, Antineoplastic Agents, MESH: Cyclin-Dependent Kinase 9, Cell Line, Structure-Activity Relationship, 03 medical and health sciences, Cyclin-dependent kinase, Cell Line, Tumor, Spheroids, Cellular, Humans, Structure–activity relationship, [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology, [ SDV.BBM ] Life Sciences [q-bio]/Biochemistry, Molecular Biology, 030304 developmental biology, Aza Compounds, MESH: Humans, 010405 organic chemistry, MESH : Cell Line, Tumor, MESH: Apoptosis, Cyclin-Dependent Kinase 2, Cyclin-dependent kinase 2, MESH : Humans, MESH: Cyclin A, Bridged Bicyclo Compounds, Heterocyclic, MESH: Crystallography, X-Ray, Cyclin-Dependent Kinase 9, In vitro, 0104 chemical sciences, MESH: Cell Line, Pyrimidines, MESH: Aza Compounds, MESH: Pyrimidines, biology.protein, MESH : Spheroids, Cellular, MESH: Antineoplastic Agents, Cyclin-dependent kinase 9, Drug Screening Assays, Antitumor, MESH : Aza Compounds, MESH : Crystallography, X-Ray, MESH : Apoptosis
Abstract: We report the synthesis and biological characterization of 3-(pyrimidin-4-yl)-7-azaindoles (meriolins), a chemical hybrid between the natural products meridianins and variolins, derived from marine organisms. Meriolins display potent inhibitory activities toward cyclin-dependent kinases (CDKs) and, to a lesser extent, other kinases (GSK-3, DYRK1A). The crystal structures of 1e (meriolin 5) and variolin B (Bettayeb, K.; Tirado, O. M.; Marionneau-Lambert, S.; Ferandin, Y.; Lozach, O.; Morris, J.; Mateo-Lozano, S.; Drückes, P.; Schächtele, C.; Kubbutat, M.; Liger, F.; Marquet, B.; Joseph, B.; Echalier, A.; Endicott, J.; Notario, V.; Meijer, L. Cancer Res. 2007, 67, 8325-8334) in complex with CDK2/cyclin A reveal that the two inhibitors are orientated in very different ways inside the ATP-binding pocket of the kinase. A structure-activity relationship provides further insight into the molecular mechanism of action of this family of kinase inhibitors. Meriolins are also potent antiproliferative and proapoptotic agents in cells cultured either as monolayers or in spheroids. Proapoptotic efficacy of meriolins correlates best with their CDK2 and CDK9 inhibitory activity. Meriolins thus constitute a promising class of pharmacological agents to be further evaluated against the numerous human diseases that imply abnormal regulation of CDKs including cancers, neurodegenerative disorders, and polycystic kidney disease.
Published: 2008
Full Text: View/download PDF

48. NOD2: a potential target for regulating liver injury

Author: Jean-Pierre Hugot, Philippe Mathurin, Sylvie Hudault, Sébastien Dharancy, Laurent Dubuquoy, Mathias Chamaillard, Filomena Conti, Pierre Desreumaux, Irene Garcia, Alexandre Louvet, Dominique Berrebi, Emilie Gantier, Philippe J. Sansonetti, Dana J. Philpott, Fabrice Chareyre, Mathilde Body-Malapel, Gilles Pagès, Marco Giovannini, Stephen E. Girardin, Physiopathologie des Maladies Inflammatoires de l'Intestin, Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille, Droit et Santé, Université de Lille, Droit et Santé, Hôpital Duriez, Service des Maladies de l'Appareil digestif et de la Nutrition, Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Service d'Anatomie et de Cytologie Pathologiques, Hôpital Robert Debré, Inflammation intestinale pathologique de l'enfant, Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM), Department of Immunology, University of Toronto, Génomique Fonctionnelle des Tumeurs Solides (U1162), Université Paris 13 (UP13)-Université Paris Diderot - Paris 7 (UPD7)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut de signalisation, biologie du développement et cancer (ISBDC), Université Nice Sophia Antipolis (1965 - 2019) (UNS), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Centre National de la Recherche Scientifique (CNRS)-Université Côte d'Azur (UCA), Department of Laboratory Medicine and Pathobiology (LMP), Université de Genève = University of Geneva (UNIGE), Pathogenes et Fonctions des Cellules Epitheliales Polarisees, Université Paris-Sud - Paris 11 (UP11)-Institut National de la Santé et de la Recherche Médicale (INSERM), Laboratoire de Biologie Cellulaire, Université Paris Descartes - Paris 5 (UPD5), Pathogénie Microbienne Moléculaire, Institut Pasteur [Paris] (IP)-Institut National de la Santé et de la Recherche Médicale (INSERM), Collège de France - Chaire Microbiologie et Maladies infectieuses, Collège de France (CdF (institution)), Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Université de Lille, Droit et Santé, Centre Hospitalier Régional Universitaire [Lille] ( CHRU Lille ), Université Paris Diderot - Paris 7 ( UPD7 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Genomique Fonctionnelle des Tumeurs Solides, Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Université Paris Descartes - Paris 5 ( UPD5 ) -IFR105-Université Paris Diderot - Paris 7 ( UPD7 ), Institut de signalisation, biologie du développement et cancer ( ISBDC ), Université Nice Sophia Antipolis ( UNS ), Université Côte d'Azur ( UCA ) -Université Côte d'Azur ( UCA ) -Centre National de la Recherche Scientifique ( CNRS ), Department of Laboratory Medicine and Pathobiology ( LMP ), Department of Pathology and Immunology, Univ. Geneva, University of Geneva [Switzerland], Université Paris-Sud - Paris 11 ( UP11 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Université Paris Descartes - Paris 5 ( UPD5 ), Institut Pasteur [Paris]-Institut National de la Santé et de la Recherche Médicale ( INSERM ), Université Nice Sophia Antipolis (... - 2019) (UNS), Université Côte d'Azur (UCA)-Université Côte d'Azur (UCA)-Centre National de la Recherche Scientifique (CNRS), Institut Pasteur [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre National de la Recherche Scientifique (CNRS)-Université Nice Sophia Antipolis (... - 2019) (UNS), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Université Côte d'Azur (UCA), Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Pasteur [Paris], and Chaire Microbiologie et Maladies infectieuses
Subjects: MESH : RNA, Messenger, MESH: Spleen, Lymphocyte, Nod2 Signaling Adaptor Protein, RNA, Messenger/metabolism, MESH: Adjuvants, Immunologic, Apoptosis, MESH : Hepatocytes, ddc:616.07, MESH : Nod2 Signaling Adaptor Protein, Interferon-gamma/analysis/pharmacology, [ SDV.CAN ] Life Sciences [q-bio]/Cancer, MESH: Hepatocytes, Mice, 0302 clinical medicine, Concanavalin A, MESH: Up-Regulation, MESH: Nod2 Signaling Adaptor Protein, MESH: Animals, MESH : Up-Regulation, MESH : Acetylmuramyl-Alanyl-Isoglutamine, Cells, Cultured, Liver injury, 0303 health sciences, Leukocytes, Mononuclear/drug effects/*immunology, MESH: Hepatitis, Animal, MESH : Interferon Type II, MESH: Case-Control Studies, 3. Good health, Up-Regulation, Acetylmuramyl-Alanyl-Isoglutamine/pharmacology, 030220 oncology & carcinogenesis, Hepatocytes/drug effects/metabolism/physiology, Muramyl dipeptide, MESH: Cells, Cultured, MESH : Case-Control Studies, Liver/*injuries, [ SDV.BBM.BM ] Life Sciences [q-bio]/Biochemistry, Molecular Biology/Molecular biology, MESH: Concanavalin A, Nod2 Signaling Adaptor Protein/analysis/*deficiency/genetics/*metabolism, Pathology and Forensic Medicine, Interferon-gamma, 03 medical and health sciences, Adjuvants, Immunologic, Humans, RNA, Messenger, Molecular Biology, MESH: Humans, Tumor Necrosis Factor-alpha, MESH : Humans, [SDV.BBM.BM]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Molecular biology, medicine.disease, digestive system diseases, Immunity, Innate, MESH : Leukocytes, Mononuclear, Mice, Inbred C57BL, chemistry, MESH: Tumor Necrosis Factor-alpha, Case-Control Studies, Immunology, Hepatitis, Animal/chemically induced/*immunology/metabolism/pathology, Leukocytes, Mononuclear, MESH : Hepatitis, Animal, MESH : Apoptosis, MESH: Liver, MESH : Immunity, Natural, Cell Separation, Hepatitis, Animal, MESH: Mice, Knockout, chemistry.chemical_compound, Adjuvants, Immunologic/pharmacology, NOD2, MESH : Concanavalin A, Tumor Necrosis Factor-alpha/analysis/pharmacology, MESH : Tumor Necrosis Factor-alpha, Mice, Knockout, MESH: Kinetics, Concanavalin A/toxicity, MESH: Leukocytes, Mononuclear, medicine.anatomical_structure, Liver, medicine.symptom, MESH : Kinetics, Acetylmuramyl-Alanyl-Isoglutamine, Cell Separation/methods, MESH : Spleen, MESH: Interferon Type II, Inflammation, [SDV.CAN]Life Sciences [q-bio]/Cancer, chemical and pharmacologic phenomena, MESH : Mice, Inbred C57BL, Biology, MESH: Cell Separation, Immune system, MESH: Mice, Inbred C57BL, MESH : Mice, MESH : Cells, Cultured, medicine, Animals, Spleen/cytology/drug effects, MESH: Mice, 030304 developmental biology, MESH: RNA, Messenger, MESH: Immunity, Natural, Hepatitis, Innate immune system, MESH: Apoptosis, MESH : Liver, Cell Biology, Kinetics, MESH: Acetylmuramyl-Alanyl-Isoglutamine, MESH : Cell Separation, Hepatocytes, MESH : Adjuvants, Immunologic, MESH : Mice, Knockout, MESH : Animals, Spleen
Abstract: The recent discovery of bacterial receptors such as NOD2 that contribute to crosstalk between innate and adaptive immune systems in the digestive tract constitutes an important challenge in our understanding of liver injury mechanisms. The present study focuses on NOD2 functions during liver injury. NOD2, TNF-alpha and IFN-gamma mRNA were quantified using real-time PCR in liver samples from patients and mice with liver injury. We evaluated the susceptibility of concanavalin A (ConA) challenge in NOD2-deficient mice (Nod2-/-) compared to wild-type littermates. We tested the effect of muramyl dipeptide (MDP), the specific activator of NOD2, on ConA-induced liver injury in C57BL/6 mice. We studied the cellular distribution and the role of NOD2 in immune cells and hepatocytes. We demonstrated that NOD2, TNF-alpha and IFN-gamma were upregulated during liver injury in mice and humans. Nod2-/- mice were resistant to ConA-induced hepatitis compared to their wild-type littermates, through reduced IFN-gamma production by immune cells. Conversely, administration of MDP exacerbated ConA-induced liver injury. MDP was a strong inducer of IFN-gamma in freshly isolated human PBMC, splenocytes and hepatocytes. Our study supports the hypothesis that NOD2 contributes to liver injury via a regulatory mechanism affecting immune cells infiltrating the liver and hepatocytes. Taken together, our results indicate that NOD2 may represent a new therapeutic target in liver diseases.
Published: 2008
Full Text: View/download PDF

49. TRAIL in cancer therapy: present and future challenges

Author: Alexandre Morizot, Olivier Micheau, Eric Solary, Delphine Merino, Najoua Lalaoui, Lipides - Nutrition - Cancer (U866) ( LNC ), Université de Bourgogne ( UB ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Ecole Nationale Supérieure de Biologie Appliquée à la Nutrition et à l'Alimentation de Dijon ( ENSBANA ), This study was supported by grants of the Ligue Nationale contre le Cancer, the Conseil Régional de Bourgogne, the INCa (Institut National du Cancer), le Cancéropôle Grand- Est, the ANR (Agence Nationale de la Recherche), and the INSERM., Micheau, Olivier, Lipides - Nutrition - Cancer (U866) (LNC), and Université de Bourgogne (UB)-Institut National de la Santé et de la Recherche Médicale (INSERM)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Ecole Nationale Supérieure de Biologie Appliquée à la Nutrition et à l'Alimentation de Dijon (ENSBANA)
Subjects: MESH: Signal Transduction, medicine.medical_treatment, Clinical Biochemistry, Apoptosis, TRAIL, TNF-Related Apoptosis-Inducing Ligand, Bioinformatics, MESH : TNF-Related Apoptosis-Inducing Ligand, 0302 clinical medicine, Drug Delivery Systems, Neoplasms, Drug Discovery, MESH: Animals, MESH: Neoplasms, 0303 health sciences, Tnf superfamily, 3. Good health, MESH : Antineoplastic Agents, Cytokine, 030220 oncology & carcinogenesis, Molecular Medicine, MESH : Drug Delivery Systems, TRAIL-Receptors, Signal transduction, MESH: TNF-Related Apoptosis-Inducing Ligand, Signal Transduction, MESH: Forecasting, Programmed cell death, MESH: Drug Delivery Systems, Cancer therapy, Antineoplastic Agents, Article, resistance, 03 medical and health sciences, medicine, [SDV.BBM] Life Sciences [q-bio]/Biochemistry, Molecular Biology, Animals, Humans, cancer, [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology, MESH : Forecasting, TRAIL-receptor agonistic antibodies, [ SDV.BBM ] Life Sciences [q-bio]/Biochemistry, Molecular Biology, 030304 developmental biology, Pharmacology, MESH : Signal Transduction, MESH: Humans, business.industry, MESH: Apoptosis, MESH : Humans, Cancer, medicine.disease, MESH : Neoplasms, Cancer cell, Immunology, MESH: Antineoplastic Agents, MESH : Animals, business, MESH : Apoptosis, Forecasting
Abstract: International audience; Since its identification in 1995, TNF-related apoptosis-inducing ligand (TRAIL) has sparked growing interest in oncology due to its reported ability to selectively trigger cancer cell death. In contrast to other members of the TNF superfamily, TRAIL administration in vivo is safe. The relative absence of toxic side effects of this naturally occurring cytokine, in addition to its antitumoural properties, has led to its preclinical evaluation. However, despite intensive investigations, little is known in regards to the mechanisms underlying TRAIL selectivity or efficiency. An appropriate understanding of its physiological relevance, and of the mechanisms controlling cancer cells escape from TRAIL-induced cell death, will be required to optimally use the cytokine in clinics. The present review focuses on recent advances in the understanding of TRAIL signal transduction and discusses the existing and future challenges of TRAIL-based cancer therapy development.
Published: 2007
Full Text: View/download PDF

50. Antigen crosspresentation by human plasmacytoid dendritic cells

Author: Diana Matheoud, Daniel Hanau, Anne Hosmalin, Olivier Schwartz, Sophie Caillat-Zucman, Jean-Gérard Guillet, Pierre Lebon, Nicoletta Casartelli, Guillaume Hoeffel, Monique Gannagé, Farhad Heshmati, Nicolas Escriou, Concepciion Maranon, Michelina Nascimbeni, Anne-Claire Ripoche, [Institut Cochin] Departement Infection, immunité, inflammation, Institut Cochin ( UM3 (UMR 8104 / U1016) ), Université Paris Descartes - Paris 5 ( UPD5 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ) -Université Paris Descartes - Paris 5 ( UPD5 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ), Institut Cochin ( UMR_S567 / UMR 8104 ), Université Paris Descartes - Paris 5 ( UPD5 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ), Génétique Moléculaire des Virus Respiratoires, Institut Pasteur [Paris]-Université Paris Diderot - Paris 7 ( UPD7 ) -Centre National de la Recherche Scientifique ( CNRS ), Université Paris Descartes - Paris 5 ( UPD5 ), Unité de Médecine Transfusionnelle, CHU Cochin [AP-HP], Immunologie, génétique et traitement des maladies métaboliques et du diabète ( UMR_S 561 ), Université Paris Descartes - Paris 5 ( UPD5 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Virus et Immunité, Institut Pasteur [Paris]-Centre National de la Recherche Scientifique ( CNRS ), Biologie des Cellules Dendritiques Humaines, EFS-Cancéropôle du Grand Est-Université Louis Pasteur - Strasbourg I-Institut National de la Santé et de la Recherche Médicale ( INSERM ), Institut Cochin (IC UM3 (UMR 8104 / U1016)), Centre National de la Recherche Scientifique (CNRS)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut Cochin (UMR_S567 / UMR 8104), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Institut Pasteur [Paris]-Université Paris Diderot - Paris 7 (UPD7)-Centre National de la Recherche Scientifique (CNRS), Université Paris Descartes - Paris 5 (UPD5), Hôpital Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Immunologie, génétique et traitement des maladies métaboliques et du diabète (UMR_S 561), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre National de la Recherche Scientifique (CNRS)-Institut Pasteur [Paris], EFS-Cancéropôle du Grand Est-Université Louis Pasteur - Strasbourg I-Institut National de la Santé et de la Recherche Médicale (INSERM), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Institut Pasteur [Paris] (IP)-Université Paris Diderot - Paris 7 (UPD7)-Centre National de la Recherche Scientifique (CNRS), Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS), Centre National de la Recherche Scientifique (CNRS)-Université Paris Diderot - Paris 7 (UPD7)-Institut Pasteur [Paris], Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Descartes - Paris 5 (UPD5), and Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Descartes - Paris 5 (UPD5)
Subjects: MICROBIO, Myeloid, MESH : HIV Antigens, HIV Antigens, MESH : Leukocytes, MESH : HIV, Apoptosis, CD8-Positive T-Lymphocytes, Lymphocyte Activation, 0302 clinical medicine, Leukocytes, Immunology and Allergy, MESH: Microscopy, Confocal, Cells, Cultured, AIDS Vaccines, Antigen Presentation, 0303 health sciences, Microscopy, Confocal, MESH: Dendritic Cells, MESH: HIV, hemic and immune systems, MESH : CD8-Positive T-Lymphocytes, MESH: Lipoproteins, MESH: CD8-Positive T-Lymphocytes, Cell biology, Infectious Diseases, medicine.anatomical_structure, MESH : Antigen Presentation, MESH : Transfection, MESH: Cells, Cultured, Endosome, MESH : AIDS Vaccines, Lipoproteins, T cell, Phagocytosis, Immunology, Antigen presentation, MESH : Lipoproteins, Biology, Transfection, MESH: Leukocytes, 03 medical and health sciences, MESH: AIDS Vaccines, Antigen, MESH : Cells, Cultured, medicine, Humans, MESH: Lymphocyte Activation, MESH : Microscopy, Confocal, MESH : Lymphocyte Activation, 030304 developmental biology, MESH: Humans, MESH: Transfection, MESH: Apoptosis, MESH : Humans, HIV, Dendritic Cells, CELLIMMUNO, MESH : Dendritic Cells, MESH: Antigen Presentation, MESH: HIV Antigens, CD8, MESH : Apoptosis, 030215 immunology
Abstract: International audience; Crosspresentation is a specialized function of myeloid dendritic cells (mDCs), allowing them to induce CD8+ T cell responses against exogenous antigens that are not directly produced in their cytotosol. Human plasmacytoid DCs (pDCs) are not considered so far as able to perform crosspresentation. We showed here that purified human pDCs crosspresented vaccinal lipopeptides and HIV-1 antigens from apoptotic cells to specific CD8+ T lymphocytes. Apoptotic debris were internalized by phagocytosis and the lipopeptide LPPol reached nonacidic endosomes. This crosspresentation was amplified upon influenza virus infection. Importantly, the efficiency of crosspresentation by pDCs was comparable to that of mDCs. This property of human pDCs needs to be taken into account to understand the pathogenesis of infectious, allergic, or autimmune diseases and to help achieve desired responses during vaccination by targeting specifically either type of DCs.
Published: 2007
Full Text: View/download PDF

Catalog

Books, media, physical & digital resources

See catalog results

Searchworks

Select search scope, currently: Articles Catalog books, media & more in Jio Institute collections Articles journal articles & other e-resources

Search

Search Constraints

Refine your results

Search Limiters

Topic

Publication Year Range

Language

Journal

Database

Publisher

73 results on '"MESH : Apoptosis"'

Search Results

Catalog

Select search scope, currently: Articles

Catalog

books, media & more in Jio Institute collections

Articles

journal articles & other e-resources