Author: "François Delalande" / Topic: humans - Searchworks@Jio Institute Digital Library Search Results

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1. Combining label-free and label-based accurate quantifications with SWATH-MS: Comparison with SRM and PRM for the evaluation of bovine muscle type effects

Author: Brigitte Picard, Frédéric Bertrand, Joanna Bons, Muriel Bonnet, Christine Carapito, Sarah Cianférani, Marie Chion, François Delalande, Gauthier Husson, Myriam Maumy-Bertrand, Département Sciences Analytiques et Interactions Ioniques et Biomoléculaires (DSA-IPHC), Institut Pluridisciplinaire Hubert Curien (IPHC), Université de Strasbourg (UNISTRA)-Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA))-Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)-Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA))-Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Centre National de la Recherche Scientifique (CNRS), Institut de Recherche Mathématique Avancée (IRMA), Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS), Unité Mixte de Recherche sur les Herbivores - UMR 1213 (UMRH), VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Laboratoire Modélisation et Sûreté des Systèmes (LM2S), Laboratoire Informatique et Société Numérique (LIST3N), Université de Technologie de Troyes (UTT)-Université de Technologie de Troyes (UTT), French Ministry of Science INRAE-Phase Division (RefQuant project) French Proteomic Infrastructure (ProFI) ANR-10-INBS-08-03, Université de Strasbourg (UNISTRA)-Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)-Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Centre National de la Recherche Scientifique (CNRS), Université Clermont Auvergne (UCA), Institut Charles Delaunay (ICD), Université de Technologie de Troyes (UTT)-Centre National de la Recherche Scientifique (CNRS)-Université de Technologie de Troyes (UTT)-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)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Université de Technologie de Troyes (UTT), and Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)
Subjects: Swath ms, Proteome, Computer science, [SDV]Life Sciences [q-bio], Marbled meat, Computational biology, Mass spectrometry, Biochemistry, Mass Spectrometry, 03 medical and health sciences, Meat tenderness, [SDV.BBM.GTP]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN], [SDV.IDA]Life Sciences [q-bio]/Food engineering, Animals, Humans, Bovine muscle, Beef meat quality, Targeted proteomics, Molecular Biology, 030304 developmental biology, Label free, 0303 health sciences, Muscles, 030302 biochemistry & molecular biology, Selected reaction monitoring, Quantitative MS, SWATH-MS, Cattle, Data-Independent Acquisition (DIA), Biomarkers
Abstract: International audience; Mass spectrometry has proven to be a valuable tool for the accurate quantification of proteins. In this study, the performances of three targeted approaches, namely selected reaction monitoring (SRM), parallel reaction monitoring (PRM) and sequential windowed acquisition of all theoretical fragment ion mass spectra (SWATH-MS), to accurately quantify ten potential biomarkers of beef meat tenderness or marbling in a cohort of 64 muscle samples were evaluated. So as to get the most benefit out of the complete MS2 maps that are acquired in SWATH-MS, an original label-free quantification method to estimate protein amounts using an I-spline regression model was developed. Overall, SWATH-MS outperformed SRM in terms of sensitivity and dynamic range, while PRM still performed the best, and all three strategies showed similar quantification accuracies and precisions for the absolute quantification of targets of interest. This targeted picture was extended by 585 additional proteins for which amounts were estimated using the label-free approach on SWATH-MS; thus, offering a more global profiling of muscle proteomes and further insights into muscle type effect on candidate biomarkers of beef meat qualities as well as muscle metabolism.
Published: 2021

2. Ral GTPases promote breast cancer metastasis by controlling biogenesis and organ targeting of exosomes

Author: Shima Ghoroghi, Benjamin Mary, Annabel Larnicol, Nandini Asokan, Annick Klein, Naël Osmani, Ignacio Busnelli, François Delalande, Nicodème Paul, Sébastien Halary, Frédéric Gros, Laetitia Fouillen, Anne-Marie Haeberle, Cathy Royer, Coralie Spiegelhalter, Gwennan André-Grégoire, Vincent Mittelheisser, Alexandre Detappe, Kendelle Murphy, Paul Timpson, Raphaël Carapito, Marcel Blot-Chabaud, Julie Gavard, Christine Carapito, Nicolas Vitale, Olivier Lefebvre, Jacky G Goetz, Vincent Hyenne, Immuno-Rhumatologie Moléculaire, Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM), Département Sciences Analytiques et Interactions Ioniques et Biomoléculaires (DSA-IPHC), Institut Pluridisciplinaire Hubert Curien (IPHC), Université de Strasbourg (UNISTRA)-Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA))-Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)-Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA))-Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Centre National de la Recherche Scientifique (CNRS), Molécules de Communication et Adaptation des Micro-organismes (MCAM), Muséum national d'Histoire naturelle (MNHN)-Centre National de la Recherche Scientifique (CNRS), Laboratoire de biogenèse membranaire (LBM), Université de Bordeaux (UB)-Centre National de la Recherche Scientifique (CNRS), Institut des Neurosciences Cellulaires et Intégratives (INCI), Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS), Centre de Neurochimie, 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), Signaling in Oncogenesis, Angiogenesis and Permeability (CRCINA-ÉQUIPE 15), Centre de Recherche en Cancérologie et Immunologie Nantes-Angers (CRCINA), Université d'Angers (UA)-Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Université d'Angers (UA)-Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre hospitalier universitaire de Nantes (CHU Nantes), Institut de Cancérologie de Strasbourg Europe (ICANS), Garvan Institute of medical research, Centre recherche en CardioVasculaire et Nutrition = Center for CardioVascular and Nutrition research (C2VN), Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), INCa (PLBIO19-291), ANR-10-INBS-0008,ProFI,Infrastructure Française de Protéomique(2010), ANR-19-CE44-0019,PA-Box,Etude des fonctions pléiotropiques de l'acide phosphatidique dans la sécrétion régulée à l'aide d'une nouvelle boite à outils moléculaires(2019), ANR-11-INBS-0010,METABOHUB,Développement d'une infrastructure française distribuée pour la métabolomique dédiée à l'innovation(2011), Université de Strasbourg (UNISTRA)-Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)-Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Centre National de la Recherche Scientifique (CNRS), Université Bordeaux Segalen - Bordeaux 2-Centre National de la Recherche Scientifique (CNRS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Centre National de la Recherche Scientifique (CNRS)-Université d'Angers (UA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Centre National de la Recherche Scientifique (CNRS)-Université d'Angers (UA), The Garvan Institute of Medical Research [Sydney, Australia], Bernardo, Elizabeth, Infrastructure Française de Protéomique - - ProFI2010 - ANR-10-INBS-0008 - INBS - VALID, Etude des fonctions pléiotropiques de l'acide phosphatidique dans la sécrétion régulée à l'aide d'une nouvelle boite à outils moléculaires - - PA-Box2019 - ANR-19-CE44-0019 - AAPG2019 - VALID, and Développement d'une infrastructure française distribuée pour la métabolomique dédiée à l'innovation - - METABOHUB2011 - ANR-11-INBS-0010 - INBS - VALID
Subjects: pre-metastatic niche, QH301-705.5, Science, Aucun, Breast Neoplasms, [SDV.CAN]Life Sciences [q-bio]/Cancer, Exosomes, GTP Phosphohydrolases, Mice, [SDV.CAN] Life Sciences [q-bio]/Cancer, cell biology, Human Umbilical Vein Endothelial Cells, Animals, Humans, exosome, human, Neoplasm Metastasis, Biology (General), mouse, cancer biology, Multivesicular Bodies, zebrafish, Medicine, inserm-03103515, Research Article, Ral GTPase
Abstract: International audience; Cancer extracellular vesicles (EVs) shuttle at distance and fertilize pre-metastatic niches facilitating subsequent seeding by tumor cells. However, the link between EV secretion mechanisms and their capacity to form pre-metastatic niches remains obscure. Using mouse models, we show that GTPases of the Ral family control, through the phospholipase D1, multi-vesicular bodies homeostasis and tune the biogenesis and secretion of pro-metastatic EVs. Importantly, EVs from RalA or RalB depleted cells have limited organotropic capacities in vivo and are less efficient in promoting metastasis. RalA and RalB reduce the EV levels of the adhesion molecule MCAM/CD146, which favors EV-mediated metastasis by allowing EVs targeting to the lungs. Finally, RalA, RalB and MCAM/CD146, are factors of poor prognosis in breast cancer patients. Altogether, our study identifies RalGTPases as central molecules linking the mechanisms of EVs secretion and cargo loading to their capacity to disseminate and induce pre-metastatic niches in a CD146 dependent manner.
Published: 2021

3. Zika virus enhances monocyte adhesion and transmigration favoring viral dissemination to neural cells

Author: Emma Partiot, Nilda Vanesa Ayala-Nunez, Jacky G. Goetz, Gautier Follain, Judith R.E. Roels, Anita Eckly, Béatrice Uring-Lambert, Maxime Chazal, Raphael Gaudin, Gillian Hale, Frank M. J. Jacobs, Sandrine Bourdoulous, Orestis Faklaris, Sherif R. Zaki, Aurélie Hirschler, Nolwenn Jouvenet, Margot Carocci, Florian Bakoa, Sarah Cianférani, Christine Carapito, Frédéric Doussau, Brigid C. Bollweg, François Delalande, Institut de Recherche en Infectiologie de Montpellier (IRIM), Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), Université de Strasbourg (UNISTRA), Institut National de la Santé et de la Recherche Médicale (INSERM), Immuno-Rhumatologie Moléculaire, Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Strasbourg (UNISTRA), Fédération de Médecine Translationnelle de Strasbourg (FMTS), Département Sciences Analytiques et Interactions Ioniques et Biomoléculaires (DSA-IPHC), Institut Pluridisciplinaire Hubert Curien (IPHC), Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS)-Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS), Centers for Disease Control and Prevention [Atlanta] (CDC), Centers for Disease Control and Prevention, Swammerdam Institute for Life Sciences, University of Amsterdam [Amsterdam] (UvA)-Center for Neurosciences, Génomique virale et vaccination, Centre National de la Recherche Scientifique (CNRS)-Institut Pasteur [Paris], Université Paris Descartes - Paris 5 (UPD5), Institut Cochin (IC UM3 (UMR 8104 / U1016)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université de Paris (UP), BioCampus Montpellier (BCM), Université Montpellier 1 (UM1)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), Biologie et pharmacologie des plaquettes sanguines: hémostase, thrombose, transfusion, Université de Strasbourg (UNISTRA)-EFS-Institut National de la Santé et de la Recherche Médicale (INSERM), Les Hôpitaux Universitaires de Strasbourg (HUS), Institut des Neurosciences Cellulaires et Intégratives (INCI), Université Louis Pasteur - Strasbourg I-Centre National de la Recherche Scientifique (CNRS), This work has received funding from the French State via the French National Research Agency (ANR) as part of the program Investissements d’avenir (IdEx Université de Strasbourg) to RG. This work was supported by an ATIP-AVENIR starting grant to RG. The research leading to these results has received funding from the People Program (Marie Curie Actions) of the European Union’s Seventh Framework Program (FP7/2007–2013) under REA grant agreement no. PCOFUND-GA-2013-609102, through the PRESTIGE program coordinated by Campus France, and from the French Agency for Research on AIDS and Viral Hepatitis (ANRS), both attributed to NVAN. Experiments conducted by G.F. and J.G.G. were funded by Plan Cancer (OptoMetaTrap), Ligue contre le Cancer, Idex Attractivités (University of Strasbourg), and by institutional funds from INSERM and University of Strasbourg. G.F. was supported by a doctoral fellowship from Ligue Contre le Cancer. Mass spectrometry experiments were supported by the French Proteomic Infrastructure (ProFI, ANR-10-INBS-08-03). F.B. is a recipient of a PhD grant provided by ANRT (Association Nationale de la Recherche et de la Technologie). N.J. is funded by Agence Nationale pour la Recherche (ANR-16-CE15-0025-01), Centre National de la Recherche Scientifique (CNRS), and Institut Pasteur. CDC contributions to this paper written and edited by G.L.H. and B.C.B. in their private capacity. No official support or endorsement by the Centers for Disease Control and Prevention, Department of Health and Human Services is intended, nor should be inferred. All authors read, provided feedback, and approved the paper. The findings and conclusions in this report are those of the authors and do not necessarily represent the official position of the Centers for Disease Control and Prevention. The following reagent was obtained through the NIH AIDS Reagent Program, Division of AIDS, NIAID, NIH: HIV-1 NL4-3 AD8 Infectious Molecular Clone (pNL(AD8)) from Dr. Eric O. Freed (cat# 11346)., ANR-16-CE15-0025,Viro-Storm,Mécanismes de production incontrôlée de cytokines au cours de l'infection virale(2016), European Project: 609102,EC:FP7:PEOPLE,FP7-PEOPLE-2013-COFUND,PRESTIGE(2014), Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université de Strasbourg (UNISTRA)-Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA))-Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)-Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA))-Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Centre National de la Recherche Scientifique (CNRS), Institut Pasteur [Paris] (IP)-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 Cité (UPCité), BioCampus (BCM), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), Université de Strasbourg (UNISTRA)-Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)-Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Centre National de la Recherche Scientifique (CNRS), Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS), EFS-Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM), jouvenet, nolwenn, Mécanismes de production incontrôlée de cytokines au cours de l'infection virale - - Viro-Storm2016 - ANR-16-CE15-0025 - AAPG2016 - VALID, PRES Towards International Gain of Excellence - PRESTIGE - - EC:FP7:PEOPLE2014-09-01 - 2019-08-31 - 609102 - VALID, Equipe Direction scientifique, Sciences et Technologies de la Musique et du Son (STMS), Université Pierre et Marie Curie - Paris 6 (UPMC)-IRCAM-Centre National de la Recherche Scientifique (CNRS)-Université Pierre et Marie Curie - Paris 6 (UPMC)-IRCAM-Centre National de la Recherche Scientifique (CNRS), École pratique des hautes études (EPHE), Neuro-Immunologie Virale, Virologie UMR1161 (VIRO), École nationale vétérinaire d'Alfort (ENVA)-Institut National de la Recherche Agronomique (INRA)-Agence nationale de sécurité sanitaire de l'alimentation, de l'environnement et du travail (ANSES), Laboratoire de Photonique Quantique et Moléculaire (LPQM), Centre National de la Recherche Scientifique (CNRS)-CentraleSupélec-École normale supérieure - Cachan (ENS Cachan), Biologie et pharmacologie des plaquettes sanguines: hémostase, thrombose, transfusion (http://www.u949.inserm.fr/), Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-EFS, Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS), Laboratoire de Spectrométrie de Masse BioOrganique, Département des Sciences Analytiques, Institut Pluridisciplinaire Hubert Curien, Strasbourg, France (LSMBO-DSA-IPHC), Centre National de la Recherche Scientifique (CNRS), Immunorhumathologie moléculaire, Centre National de la Recherche Scientifique (CNRS)-Université de Montpellier (UM), and Molecular Neuroscience (SILS, FNWI)
Subjects: Central Nervous System, 0301 basic medicine, MESH: Neurons, General Physics and Astronomy, MESH: Organoids, MESH: Monocytes, Monocytes, Zika virus, 0302 clinical medicine, MESH: Transendothelial and Transepithelial Migration, Cerebellum, MESH: Animals, lcsh:Science, MESH: Embryonic Stem Cells, ComputingMilieux_MISCELLANEOUS, Zebrafish, [SDV.MP.VIR] Life Sciences [q-bio]/Microbiology and Parasitology/Virology, Neurons, Multidisciplinary, Zika Virus Infection, Cell adhesion molecule, food and beverages, Sciences du Vivant [q-bio]/Microbiologie et Parasitologie, Phenotype, 3. Good health, Cell biology, Organoids, Mechanisms of disease, medicine.anatomical_structure, MESH: Cell Survival, [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology, Female, Endothelium, Cell Survival, Science, MESH: Zika Virus, Biology, MESH: Endothelium, Article, General Biochemistry, Genetics and Molecular Biology, Virus, MESH: Cell Adhesion, 03 medical and health sciences, Virology, medicine, Animals, Humans, MESH: Central Nervous System, Cellular microbiology, Cell adhesion, MESH: Zebrafish, Embryonic Stem Cells, MESH: Humans, Monocyte, fungi, Transendothelial and Transepithelial Migration, Zika Virus, General Chemistry, biology.organism_classification, Embryonic stem cell, MESH: Cerebellum, Disease Models, Animal, 030104 developmental biology, lcsh:Q, MESH: Disease Models, Animal, Cell Adhesion Molecules, MESH: Female, 030217 neurology & neurosurgery
Abstract: Zika virus (ZIKV) invades and persists in the central nervous system (CNS), causing severe neurological diseases. However the virus journey, from the bloodstream to tissues through a mature endothelium, remains unclear. Here, we show that ZIKV-infected monocytes represent suitable carriers for viral dissemination to the CNS using human primary monocytes, cerebral organoids derived from embryonic stem cells, organotypic mouse cerebellar slices, a xenotypic human-zebrafish model, and human fetus brain samples. We find that ZIKV-exposed monocytes exhibit higher expression of adhesion molecules, and higher abilities to attach onto the vessel wall and transmigrate across endothelia. This phenotype is associated to enhanced monocyte-mediated ZIKV dissemination to neural cells. Together, our data show that ZIKV manipulates the monocyte adhesive properties and enhances monocyte transmigration and viral dissemination to neural cells. Monocyte transmigration may represent an important mechanism required for viral tissue invasion and persistence that could be specifically targeted for therapeutic intervention., Zika virus (ZIKV) can infect the central nervous system, but it is not clear how it reaches the brain. Here, Ayala-Nunez et al. show in ex vivo and in vivo models that ZIKV can hitch a ride in monocytes in a Trojan Horse manner to cross the endothelium and disseminate the virus.
Published: 2019

4. Post-Translational Regulation of the Glucose-6-Phosphatase Complex by Cyclic Adenosine Monophosphate Is a Crucial Determinant of Endogenous Glucose Production and Is Controlled by the Glucose-6-Phosphate Transporter

Author: Maud Soty, Gilles Mithieux, François Delalande, Carine Zitoun, Julien Chilloux, Amandine Gautier-Stein, Fabrice Bertile, Nutrition, diabète et cerveau, Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut Pluridisciplinaire Hubert Curien (IPHC), Université de Strasbourg (UNISTRA)-Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Centre National de la Recherche Scientifique (CNRS), Di Carlo, Marie-Ange, and Nutrition, diabète et cerveau (NUDICE)
Subjects: 0301 basic medicine, post-translational modification (PTM), Biochemistry, Antiporters, chemistry.chemical_compound, Cyclic AMP, Phosphorylation, ADCY6, glucose-6-phosphatase, Forskolin, Type 2 diabetes, Hep G2 Cells, Biological Sciences, ADCY3, [SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], Glucose 6-phosphatase, Signal Transduction, Biochemistry & Molecular Biology, Monosaccharide Transport Proteins, Genetic Vectors, Glucose-6-Phosphate, Biology, Glucagon, Cell Line, 03 medical and health sciences, Animals, Humans, Cyclic adenosine monophosphate, [SDV.NEU] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], Protein kinase A, Adenoviruses, Human, glucose-6-phosphate transporter, Colforsin, Epithelial Cells, General Chemistry, Cyclic AMP-Dependent Protein Kinases, Rats, Protein Subunits, Glucose, gluconeogenesis, 030104 developmental biology, Gene Expression Regulation, glucagon, chemistry, Glucose 6-phosphate, Protein Biosynthesis, Chemical Sciences, Mutagenesis, Site-Directed, biology.protein, protein kinase A, Caco-2 Cells
Abstract: International audience; The excessive endogenous glucose production (EGP) induced by glucagon participates in the development of type 2 diabetes. To further understand this hormonal control, we studied the short-term regulation by cyclic adenosine monophosphate (cAMP) of the glucose-6-phosphatase (G6Pase) enzyme, which catalyzes the last reaction of EGP. In gluconeogenic cell models, a 1-h treatment by the adenylate cyclase activator forskolin increased G6Pase activity and glucose production independently of any change in enzyme protein amount or G6P content. Using specific inhibitors or protein overexpression, we showed that the stimulation of G6Pase activity involved the protein kinase A (PKA). Results of site-directed mutagenesis, mass spectrometry analyses, and in vitro phosphorylation experiments suggested that the PKA stimulation of G6Pase activity did not depend on a direct phosphorylation of the enzyme. However, the temperature-dependent induction of both G6Pase activity and glucose release suggested a membrane-based mechanism. G6Pase is composed of a G6P transporter (G6PT) and a catalytic unit (G6PC). Surprisingly, we demonstrated that the increase in G6PT activity was required for the stimulation of G6Pase activity by forskolin. Our data demonstrate the existence of a post-translational mechanism that regulates G6Pase activity and reveal the key role of G6PT in the hormonal regulation of G6Pase activity and of EGP.Erratum inCorrection to "Post-Translational Regulation of the Glucose-6-Phosphatase Complex by Cyclic Adenosine Monophosphate Is a Crucial Determinant of Endogenous Glucose Production and Is Controlled by the Glucose-6-Phosphate Transporter". [J Proteome Res. 2016]PMID: 27111186 DOI: 10.1021/acs.jproteome.6b00284
Published: 2016

5. The ESCRT-III Protein CHMP1A Mediates Secretion of Sonic Hedgehog on a Distinctive Subtype of Extracellular Vesicles

Author: Song Pang, Frank M. J. Jacobs, Michael E. Coulter, Raphael Gaudin, C. Shan Xu, Gerrald A Lodewijk, Ganeshwaran H. Mochida, Sarah Cianférani, Harald F. Hess, Wei-Chung Allen Lee, Christopher A. Walsh, Tomas Kirchhausen, Dilenny M. Gonzalez, Monica L. Calicchio, François Delalande, Edward Yang, Cristina M. Dorobantu, Richard S. Smith, Hart G.W. Lidov, David Haussler, Eric T. Wong, Vijay S. Ganesh, Maria K. Lehtinen, Elaine T. Lim, Thorsten M. Schlaeger, Molecular Neuroscience (SILS, FNWI), Equipe Direction scientifique, Sciences et Technologies de la Musique et du Son (STMS), Institut de Recherche et Coordination Acoustique/Musique (IRCAM)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche et Coordination Acoustique/Musique (IRCAM)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS), Département Sciences Analytiques et Interactions Ioniques et Biomoléculaires (DSA-IPHC), Institut Pluridisciplinaire Hubert Curien (IPHC), Université de Strasbourg (UNISTRA)-Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)-Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Centre National de la Recherche Scientifique (CNRS), Computer Science and Artificial Intelligence Laboratory [Cambridge] (CSAIL), Massachusetts Institute of Technology (MIT), McMaster Univ, Med Phys & Appl Radiat Sci Dept, Hamilton, ON L8S 4K1, Canada, Analytic and Translational Genetics Unit, Department of Medicine, Massachusetts General Hospital and Harvard Medical School, Harvard Medical School [Boston] (HMS), Center for Biomolecular Science and Engineering, University of California [Santa Cruz] (UCSC), and University of California-University of California
Subjects: 0301 basic medicine, [SDV]Life Sciences [q-bio], Medical Physiology, Vesicular Transport Proteins, Aucun, Mice, 0302 clinical medicine, microcephaly, Sonic hedgehog, Pediatric, biology, neurodevelopment, Chemistry, Brain, Cell biology, Stem Cell Research - Nonembryonic - Non-Human, Adult, Endosome, 1.1 Normal biological development and functioning, Pontocerebellar hypoplasia, CHMP1A, Sciences du Vivant [q-bio]/Médecine humaine et pathologie, Article, General Biochemistry, Genetics and Molecular Biology, ESCRT, multivesicular body, 03 medical and health sciences, Extracellular Vesicles, sonic hedgehog, Rare Diseases, Clinical Research, Underpinning research, medicine, Animals, Humans, Secretion, Hedgehog Proteins, Progenitor, Endosomal Sorting Complexes Required for Transport, Infant, Newborn, Neurosciences, Infant, medicine.disease, Newborn, Stem Cell Research, Brain Disorders, 030104 developmental biology, Choroid Plexus, biology.protein, NIH 3T3 Cells, Congenital Structural Anomalies, Biochemistry and Cell Biology, 030217 neurology & neurosurgery, RAB18, Biogenesis
Abstract: SUMMARY Endosomal sorting complex required for transport (ESCRT) complex proteins regulate biogenesis and release of extracellular vesicles (EVs), which enable cell-to-cell communication in the nervous system essential for development and adult function. We recently showed human loss-of-function (LOF) mutations in ESCRT-III member CHMP1A cause autosomal recessive microcephaly with pontocerebellar hypoplasia, but its mechanism was unclear. Here, we show Chmp1a is required for progenitor proliferation in mouse cortex and cerebellum and progenitor maintenance in human cerebral organoids. In Chmp1a null mice, this defect is associated with impaired sonic hedgehog (Shh) secretion and intraluminal vesicle (ILV) formation in multivesicular bodies (MVBs). Furthermore, we show CHMP1A is important for release of an EV subtype that contains AXL, RAB18, and TMED10 (ART) and SHH. Our findings show CHMP1A loss impairs secretion of SHH on ART-EVs, providing molecular mechanistic insights into the role of ESCRT proteins and EVs in the brain., Graphical Abstract, In Brief Extracellular vesicles (EVs) are essential for cell-to-cell communication in developing brain. Coulter et al. show that the human microcephaly gene CHMP1A is required for neuroprogenitor proliferation through regulation of vesicular secretion of the growth factor sonic hedgehog (SHH). CHMP1A specifically impairs SHH secretion on a distinctive EV subtype, ART-EV.
Published: 2018

6. Validating Missing Proteins in Human Sperm Cells by Targeted Mass-Spectrometry- and Antibody-based Methods

Author: Yves Vandenbrouck, Charlotte Macron, Thomas Fréour, Lydie Lane, Karine Rondel, Charles Pineau, Paula D. Duek, François Delalande, Christine Carapito, Marine Seffals, Cecilia Lindskog, Institut Pluridisciplinaire Hubert Curien (IPHC), Université de Strasbourg (UNISTRA)-Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA))-Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Centre National de la Recherche Scientifique (CNRS), Swiss Institute of Bioinformatics [Genève] (SIB), H2P2 - Histo Pathologie Hight Precision (H2P2), Université de Rennes (UR)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Institut de recherche en santé, environnement et travail (Irset), Université d'Angers (UA)-Université de Rennes (UR)-École des Hautes Études en Santé Publique [EHESP] (EHESP)-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 ), Uppsala University, Centre hospitalier universitaire de Nantes (CHU Nantes), Centre de Recherche en Transplantation et Immunologie (U1064 Inserm - CRTI), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN), Commissariat à l'énergie atomique et aux énergies alternatives (CEA), Laboratoire de Biologie à Grande Échelle (BGE - UMR S1038), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Institut de Recherche Interdisciplinaire de Grenoble (IRIG), Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA), Université Grenoble Alpes [2016-2019] (UGA [2016-2019]), Swiss Institute of Bioinformatics [Lausanne] (SIB), Université de Lausanne = University of Lausanne (UNIL), French National Agency for Research (ANR) [ANR-10-INBS-08], Biogenouest, Infrastructures en Biologie Sante et Agronomie (IBiSA), Conseil Regional de Bretagne, ANR-10-INBS-0008,ProFI,Infrastructure Française de Protéomique(2010), Université de Strasbourg (UNISTRA)-Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Centre National de la Recherche Scientifique (CNRS), 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), Université d'Angers (UA)-Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-École des Hautes Études en Santé Publique [EHESP] (EHESP)-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 ), Institut de Recherche Interdisciplinaire de Grenoble (IRIG), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019]), Université de Lausanne (UNIL), Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS), Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique )-Institut National de la Santé et de la Recherche Médicale (INSERM)-École des Hautes Études en Santé Publique [EHESP] (EHESP)-Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Université d'Angers (UA), Sciences Analytiques et Interactions Ioniques et Biomoléculaires (DSA-IPHC), Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS), Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS), Foie, métabolismes et cancer, 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 ), Equipe Direction scientifique, Sciences et Technologies de la Musique et du Son (STMS), Université Pierre et Marie Curie - Paris 6 (UPMC)-IRCAM-Centre National de la Recherche Scientifique (CNRS)-Université Pierre et Marie Curie - Paris 6 (UPMC)-IRCAM-Centre National de la Recherche Scientifique (CNRS), Etude de la dynamique des protéomes (EDyP), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Grenoble Alpes (UGA)-Institut de Recherche Interdisciplinaire de Grenoble (IRIG), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Grenoble Alpes (UGA)-Institut de Recherche Interdisciplinaire de Grenoble (IRIG), Département de science des protéines humaines [Genève], Université de Genève (UNIGE)-Faculté de médecine [Genève], Groupe d'Etude de la Reproduction Chez l'Homme et les Mammiferes (GERHM), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-IFR140-Institut National de la Santé et de la Recherche Médicale (INSERM), Jonchère, Laurent, and Infrastructure Française de Protéomique - - ProFI2010 - ANR-10-INBS-0008 - INBS - VALID
Subjects: 0301 basic medicine, Male, Proteome, [SDV]Life Sciences [q-bio], Tandem mass spectrometry, Biochemistry, immunocytochemistry, Tandem Mass Spectrometry, Testis, Human proteome project, ComputingMilieux_MISCELLANEOUS, ddc:616, biology, Histocytochemistry, bioinformatics, Immunohistochemistry, Spermatozoa, [SDV] Life Sciences [q-bio], spermatozoon, Chromosomes, Human, Pair 2, immunohistochemistry, Antibody, missing proteins, Human, human proteome project, targeted proteomics, Octoxynol, Human Protein Atlas, Context (language use), Computational biology, Chromosomes, Antibodies, 03 medical and health sciences, Spermatozoa/chemistry, Proteome/analysis, Humans, Chromosomes, Human, Pair 14, 030102 biochemistry & molecular biology, Testis/chemistry, General Chemistry, data mining, Sperm, Molecular biology, parallel reaction monitoring, 030104 developmental biology, Targeted mass spectrometry, biology.protein, Pair 14/genetics, Pair 2/genetics
Abstract: The present study is a contribution to the "neXt50 challenge", a coordinated effort across C-HPP teams to identify the 50 most tractable missing proteins (MPs) on each chromosome. We report the targeted search of 38 theoretically detectable MPs from chromosomes 2 and 14 in Triton X-100 soluble and insoluble sperm fractions from a total of 15 healthy donors. A targeted mass-spectrometry-based strategy consisting of the development of LC-PRM assays (with heavy labeled synthetic peptides) targeting 92 proteotypic peptides of the 38 selected MPs was used. Out of the 38 selected MPs, 12 were identified with two or more peptides and 3 with one peptide after extensive SDS-PAGE fractionation of the two samples and with overall low-intensity signals. The PRM data are available via ProteomeXchange in PASSEL (PASS01013). Further validation by immunohistochemistry on human testes sections and cytochemistry on sperm smears was performed for eight MPs with antibodies available from the Human Protein Atlas. Deep analysis of human sperm still allows the validation of MPs and therefore contributes to the C-HPP worldwide effort. We anticipate that our results will be of interest to the reproductive biology community because an in-depth analysis of these MPs may identify potential new candidates in the context of human idiopathic infertilities.
Published: 2017

7. FACTORS INFLUENCING REIMBURSEMENT OF MEDICAL DEVICES IN FRANCE

Author: Marie-Christine Reymond, Sylvia Germain, François Delalande, and Pierre Loge
Subjects: medicine.medical_specialty, Technology Assessment, Biomedical, Multivariate analysis, media_common.quotation_subject, Technical standard, 030209 endocrinology & metabolism, Reimbursement Mechanisms, 03 medical and health sciences, Government Agencies, 0302 clinical medicine, Humans, Medicine, Quality (business), 030212 general & internal medicine, Reimbursement, media_common, business.industry, Health Policy, Univariate, Evidence-based medicine, Clinical trial, Equipment and Supplies, Family medicine, France, business, Inclusion (education)
Abstract: Objectives: This study aims to analyze the key factors considered for the first application of the National Committee for the Evaluation of Medical Devices (CNEDiMTS) for achieving reimbursement through registration in the list of products and services qualifying for reimbursement (LPPR).Methods: All the appraisals studied on medical devices (MD) for first inclusion in the LPPR during 2011 and 2012 were retrieved from the French National Authority for Health or Haute Autorité de santé (HAS) Web site. A list of relevant factors was analyzed for each included opinion, followed by univariate and multivariate analyses to highlight the key factors that impacted the expected benefit (EB) provided by HAS.Results: A total of 151 appraisals were included in the study. Of them, 94 (62 percent) were granted with sufficient EB. The manufacturers were mostly from the United States (36 percent), while most of the applicants were from France (84 percent). After adjusting for other retrieved factors, it was observed that MDs complying with the technical standards, requests supported by opinion(s) from previous generation of MD, and the presence of recommendations or guidelines had more probability to obtain a sufficient EB. A lower probability was related to MDs supported by low-quality studies and with no specific health public benefit.Conclusions: Our results confirmed that manufacturers seeking reimbursement should be aware of the expectations of the health authorities (level of evidence, technical standard, etc.) and foresee their plan of sending requests for funding so that they can provide evidence of good quality.
Published: 2015

8. A ruthenium anticancer compound interacts with histones and impacts differently on epigenetic and death pathways compared to cisplatin

Author: Cynthia Licona, François Delalande, Moussa Ali, Marie-Elodie Spaety, Georg Mellitzer, John Spencer, Christian Gaiddon, Antonelle Capuozzo, Sarah Cianférani, Alain Van Dorsselaer, Rita Santamaria, Olivier Armant, Michel Pfeffer, Licona, Cynthia, Spaety, Marie Elodie, Capuozzo, Antonella, Ali, Moussa, Santamaria, Rita, Armant, Olivier, Delalande, Francoi, Van Dorsselaer, Alain, Cianferani, Sarah, Spencer, John, Pfeffer, Michel, Mellitzer, Georg, Gaiddon, Christian, INSERM 1113 Voies de signalisation du développement et du stress cellulaire dans les cancers digestifs et urologiques, 'Federico II' University of Naples Medical School, Institut de Chimie de Strasbourg, Université de Strasbourg (UNISTRA)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Karlsruhe Institute of Technology (KIT), Département Sciences Analytiques et Interactions Ioniques et Biomoléculaires (DSA-IPHC), Institut Pluridisciplinaire Hubert Curien (IPHC), Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS)-Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS), Department of Chemistry, School of Life Sciences, University of Sussex, and Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS)-Institut de Chimie du CNRS (INC)
Subjects: 0301 basic medicine, p53, Aucun, cisplatin, Sciences du Vivant [q-bio]/Cancer, Epigenesis, Genetic, Histones, 0302 clinical medicine, Neoplasms, Gene expression, Gene Regulatory Networks, biology, Epigenetic, Endoplasmic Reticulum Stress, Ruthenium, Gene Expression Regulation, Neoplastic, Histone, Oncology, Biochemistry, 030220 oncology & carcinogenesis, ER stre, Signal transduction, ER stress, Research Paper, QD0241, medicine.drug, Life sciences, Cell Survival, chemistry.chemical_element, 03 medical and health sciences, Histone H3, Cell Line, Tumor, ddc:570, Organometallic Compounds, medicine, Humans, [CHIM]Chemical Sciences, Epigenetics, ruthenium, Cell Proliferation, QD0415, Cisplatin, epigenetics, Gene Expression Profiling, HCT116 Cells, 030104 developmental biology, chemistry, biology.protein, Histone deacetylase, QD0146
Abstract: Ruthenium complexes are considered as potential replacements for platinum compounds in oncotherapy. Their clinical development is handicapped by a lack of consensus on their mode of action. In this study, we identify three histones (H3.1, H2A, H2B) as possible targets for an anticancer redox organoruthenium compound (RDC11). Using purified histones, we confirmed an interaction between the ruthenium complex and histones that impacted on histone complex formation. A comparative study of the ruthenium complex versus cisplatin showed differential epigenetic modifications on histone H3 that correlated with differential expression of histone deacetylase (HDAC) genes. We then characterized the impact of these epigenetic modifications on signaling pathways employing a transcriptomic approach. Clustering analyses showed gene expression signatures specific for cisplatin (42%) and for the ruthenium complex (30%). Signaling pathway analyses pointed to specificities distinguishing the ruthenium complex from cisplatin. For instance, cisplatin triggered preferentially p53 and folate biosynthesis while the ruthenium complex induced endoplasmic reticulum stress and trans-sulfuration pathways. To further understand the role of HDACs in these regulations, we used suberanilohydroxamic acid (SAHA) and showed that it synergized with cisplatin cytotoxicity while antagonizing the ruthenium complex activity. This study provides critical information for the characterization of signaling pathways differentiating both compounds, in particular, by the identification of a non-DNA direct target for an organoruthenium complex.
Published: 2017
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9. Cdx2 homeoprotein inhibits non-homologous end joining in colon cancer but not in leukemia cells

Author: Isabelle Duluc, Benjamin Renouf, Jean-Noël Freund, François Delalande, Marie Vanier, Christine Soret, Thoueiba Saandi, Isabelle Gross, Claire Domon-Dell, and Elisabeth Martin
Subjects: DNA End-Joining Repair, Ku80, Transcription, Genetic, Cell Survival, DNA repair, DNA-Activated Protein Kinase, Genome Integrity, Repair and Replication, Biology, DNA-binding protein, DNA repair complex, Cell Line, Tumor, Genetics, Humans, CDX2 Transcription Factor, Protein Interaction Domains and Motifs, CDX2, Ku Autoantigen, Transcription factor, Etoposide, Homeodomain Proteins, Leukemia, Tumor Suppressor Proteins, Antigens, Nuclear, digestive system diseases, DNA-Binding Proteins, Non-homologous end joining, Colonic Neoplasms, embryonic structures, Cancer research, Ectopic expression
Abstract: Cdx2, a gene of the paraHox cluster, encodes a homeodomain transcription factor that plays numerous roles in embryonic development and in homeostasis of the adult intestine. Whereas Cdx2 exerts a tumor suppressor function in the gut, its abnormal ectopic expression in acute leukemia is associated to a pro-oncogenic function. To try to understand this duality, we have hypothesized that Cdx2 may interact with different protein partners in the two tissues and set up experiments to identify them by tandem affinity purification. We show here that Cdx2 interacts with the Ku heterodimer specifically in intestinal cells, but not in leukemia cells, via its homeodomain. Ku proteins do not affect Cdx2 transcriptional activity. However, Cdx2 inhibits in vivo and in vitro the DNA repair activity mediated by Ku proteins in intestinal cells. Whereas Cdx2 does not affect the recruitment of Ku proteins and DNA-PKcs into the DNA repair complex, it inhibits DNA-PKcs activity. Thus, we report here a new function of Cdx2, acting as an inhibitor of the DNA repair machinery, that may contribute to its tumor suppressor function specifically in the gut.
Published: 2011

10. Differentiation between fresh and frozen–thawed sea bass (Dicentrarchus labrax) fillets using two-dimensional gel electrophoresis

Author: Guillaume Duflos, Sylvain Marlard, Valérie Lencel, Alain Van Dorsselaer, François Delalande, Alexandre Dehaut, Christine Carapito, Mylène Delosière, Thierry Grard, Pierrette Ethuin, Université du Littoral Côte d'Opale (ULCO), Qualité des Produits Animaux (QuaPA), Institut National de la Recherche Agronomique (INRA), Laboratoire de Spectrométrie de Masse BioOrganique [Strasbourg] (LSMBO), Département Sciences Analytiques et Interactions Ioniques et Biomoléculaires (DSA-IPHC), Institut Pluridisciplinaire Hubert Curien (IPHC), Université de Strasbourg (UNISTRA)-Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)-Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Centre National de la Recherche Scientifique (CNRS)-Institut Pluridisciplinaire Hubert Curien (IPHC), Université de Strasbourg (UNISTRA)-Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)-Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Centre National de la Recherche Scientifique (CNRS), Laboratoire de sécurité des aliments de Maisons-Alfort (LSAl), Agence nationale de sécurité sanitaire de l'alimentation, de l'environnement et du travail (ANSES), Région Nord-Pas-de-Calais, and Ethuin , Pierrette
Subjects: Fish Proteins, Frozen–thawed, Biogenic amines, Parvalbumins, [SDV]Life Sciences [q-bio], Food spoilage, Ingénierie des aliments, Analytical Chemistry, spectrométrie de masse, [CHIM.ANAL]Chemical Sciences/Analytical chemistry, Freezing, Animals, Humans, Food engineering, Fresh, Electrophoresis, Gel, Two-Dimensional, filet de poisson, [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology, 14. Life underwater, Sea bass, électrophorèse, gel de polyacrylamide, Polyacrylamide gel electrophoresis, congélation, Chromatography, Two-dimensional gel electrophoresis, 2D-electrophoresis, biology, decongelation, Chemistry, sea bass (dicentrarchus labrax), frozen–thawed, fresh, biogenic amines, cod Gadus-morhua, protein, muscle, fish, storage, mass-spectrometry, proteome analysis, high-pressure, quality change, parvalbumin, Sea bass (Dicentrarchus labrax), General Medicine, biology.organism_classification, amine biogène, Isoelectric point, Seafood, Total volatile, Bass, Dicentrarchus, [SDV.AEN]Life Sciences [q-bio]/Food and Nutrition, Food Science
Abstract: International audience; This study aimed to identify a protein marker that can differentiate between fresh skinless and frozen–thawed sea bass (Dicentrarchus labrax) fillets using the two-dimensional polyacrylamide gel electrophoresis (2-DE) technique. Distinct gel patterns, due to proteins with low molecular weight and low isoelectric points, distinguished fresh fillets from frozen–thawed ones. Frozen–thawed fillets showed two specific protein spots as early as the first day of the study. However, these spots were not observed in fresh fillets until at least 13 days of storage between 0 and 4 °C, fillets were judged, beyond this period, fish were unfit for human consumption as revealed by complementary studies on fish spoilage indicators namely total volatile basic nitrogen and biogenic amines. Mass spectrometry identified the specific proteins as parvalbumin isoforms. Parvalbumins may thus be useful markers of differentiation between fresh and frozen–thawed sea bass fillets.
Published: 2015

11. Rod-derived cone viability factor promotes cone survival by stimulating aerobic glycolysis

Author: Emmanuel Moyse, Emmanuelle Clérin, Géraldine Millet-Puel, Deniz Dalkara, José-Alain Sahel, Najate Aït-Ali, Frédéric Bouillaud, Anne Olivier-Bandini, Thierry Léveillard, Xavier Nicol, Alain Van Dorsselaer, Frédéric Blond, Ram Fridlich, Jacques Bellalou, Leah C. Byrne, François Delalande, Ludivine Perrocheau, Sacha Reichman, Céline Jaillard, Institut de la Vision, 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 ), Laboratoire de Spectrométrie de Masse BioOrganique (LSMBO), Helen Wills Neuroscience Institute, University of California [Berkeley], Sanofi Aventis R&D, Production de Protéines Recombinantes (Plate-Forme) ( PRPF ), Institut Pasteur [Paris]-Centre National de la Recherche Scientifique ( CNRS ), Physiologie de la reproduction et des comportements [Nouzilly] ( PRC ), Institut National de la Recherche Agronomique ( INRA ) -Institut Français du Cheval et de l'Equitation [Saumur]-Université de Tours-Centre National de la Recherche Scientifique ( CNRS ), 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 ), Sanofi, UPMC, Inserm, CNRS, EC, FFB, and ANR, 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), Laboratoire de Spectrométrie de Masse BioOrganique [Strasbourg] (LSMBO), Département Sciences Analytiques et Interactions Ioniques et Biomoléculaires (DSA-IPHC), Institut Pluridisciplinaire Hubert Curien (IPHC), Université de Strasbourg (UNISTRA)-Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)-Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Centre National de la Recherche Scientifique (CNRS)-Institut Pluridisciplinaire Hubert Curien (IPHC), Université de Strasbourg (UNISTRA)-Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)-Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Centre National de la Recherche Scientifique (CNRS), Production de Protéines Recombinantes (Plate-Forme) (PRPF), Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS), Physiologie de la reproduction et des comportements [Nouzilly] (PRC), Institut National de la Recherche Agronomique (INRA)-Institut Français du Cheval et de l'Equitation [Saumur]-Université de Tours-Centre National de la Recherche Scientifique (CNRS), 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), 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), Centre National de la Recherche Scientifique (CNRS)-Université de Tours-Institut Français du Cheval et de l'Equitation [Saumur]-Institut National de la Recherche Agronomique (INRA), Université de Strasbourg (UNISTRA)-Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA))-Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)-Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA))-Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Centre National de la Recherche Scientifique (CNRS)-Institut Pluridisciplinaire Hubert Curien (IPHC), Université de Strasbourg (UNISTRA)-Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA))-Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)-Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA))-Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Centre National de la Recherche Scientifique (CNRS), Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS), Institut National de la Recherche Agronomique (INRA)-Institut Français du Cheval et de l'Equitation [Saumur] (IFCE)-Université de Tours (UT)-Centre National de la Recherche Scientifique (CNRS), Institut National de la Recherche Agronomique (INRA)-Institut Français du Cheval et de l'Equitation [Saumur]-Université de Tours (UT)-Centre National de la Recherche Scientifique (CNRS), and Centre National de la Recherche Scientifique (CNRS)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)
Subjects: [SDV.OT]Life Sciences [q-bio]/Other [q-bio.OT], genetic structures, Glucose uptake, Mutation, Missense, Biology, Retinal Cone Photoreceptor Cells, General Biochemistry, Genetics and Molecular Biology, Retina, Mice, Thioredoxins, Retinitis pigmentosa, medicine, Animals, Humans, [ SDV.OT ] Life Sciences [q-bio]/Other [q-bio.OT], Eye Proteins, Glucose Transporter Type 1, Biochemistry, Genetics and Molecular Biology(all), Glucose transporter, medicine.disease, Alkaline Phosphatase, 3. Good health, Cell biology, Glucose, Biochemistry, Anaerobic glycolysis, biology.protein, Basigin, GLUT1, sense organs, Thioredoxin, Glycolysis, Retinitis Pigmentosa
Abstract: SummaryRod-derived cone viability factor (RdCVF) is an inactive thioredoxin secreted by rod photoreceptors that protects cones from degeneration. Because the secondary loss of cones in retinitis pigmentosa (RP) leads to blindness, the administration of RdCVF is a promising therapy for this untreatable neurodegenerative disease. Here, we investigated the mechanism underlying the protective role of RdCVF in RP. We show that RdCVF acts through binding to Basigin-1 (BSG1), a transmembrane protein expressed specifically by photoreceptors. BSG1 binds to the glucose transporter GLUT1, resulting in increased glucose entry into cones. Increased glucose promotes cone survival by stimulation of aerobic glycolysis. Moreover, a missense mutation of RdCVF results in its inability to bind to BSG1, stimulate glucose uptake, and prevent secondary cone death in a model of RP. Our data uncover an entirely novel mechanism of neuroprotection through the stimulation of glucose metabolism.
Published: 2015

12. Mapping of endogenous morphine-like compounds in the adult mouse brain: Evidence of their localization in astrocytes and GABAergic cells

Author: Denise Stuber, Yannick Goumon, Jean-Christophe Deloulme, Dominique Sage, Sylvie Dirrig-Grosch, François Delalande, Alexis Laux, Dominique Aunis, Arnaud Muller, Pierrick Poisbeau, Monique Miehe, Alain Van Dorsselaer, Physiopathologie du système nerveux., Université Louis Pasteur - Strasbourg I-IFR37-Institut National de la Santé et de la Recherche Médicale (INSERM), Département Neurotransmission et sécrétion neuroendocrine, Centre National de la Recherche Scientifique (CNRS), Plateforme imagerie cellulaire Strasbourg esplanade (Plateforme d'imagerie in vitro), Laboratoire de signalisation moléculaire et neurodégénerescence, INSERM U836, équipe 1, Physiopathologie du cytosquelette, 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), Laboratoire de Spectrométrie de Masse BioOrganique [Strasbourg] (LSMBO), Département Sciences Analytiques et Interactions Ioniques et Biomoléculaires (DSA-IPHC), Institut Pluridisciplinaire Hubert Curien (IPHC), Université de Strasbourg (UNISTRA)-Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)-Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Centre National de la Recherche Scientifique (CNRS)-Institut Pluridisciplinaire Hubert Curien (IPHC), Université de Strasbourg (UNISTRA)-Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)-Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Centre National de la Recherche Scientifique (CNRS), Plateforme d'hébergement et d'exploration fonctionnelle (Chronobiotron), Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS), INSERM CNRS Université de Strasbourg Ministère Français délégué à la Recherche et à l'Enseignement supérieur Fondation Transplantation Fondation pour la recherche médicale, Institut des Neurosciences Cellulaires et Intégratives (INCI), and Andrieux, Annie
Subjects: Male, Cerebellum, Patch-Clamp Techniques, Dopamine, MESH: Neurons, Hippocampus, Endogeny, MESH: gamma-Aminobutyric Acid, Mice, 0302 clinical medicine, Postsynaptic potential, MESH: Animals, MESH: Brain Chemistry, gamma-Aminobutyric Acid, Neurons, 0303 health sciences, Morphine, General Neuroscience, Brain, Immunohistochemistry, 3. Good health, medicine.anatomical_structure, MESH: Morphine Derivatives, GABAergic, [SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], medicine.drug, Cell type, MESH: Dopamine, [SDV.BC]Life Sciences [q-bio]/Cellular Biology, Biology, MESH: Codeine, 03 medical and health sciences, MESH: Brain, MESH: Mice, Inbred C57BL, MESH: Patch-Clamp Techniques, medicine, Animals, Humans, [SDV.NEU] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], [SDV.BC] Life Sciences [q-bio]/Cellular Biology, MESH: Mice, 030304 developmental biology, Brain Chemistry, Morphine Derivatives, MESH: Humans, Codeine, MESH: Immunohistochemistry, Morphine-6-glucuronide, MESH: Male, Olfactory bulb, Mice, Inbred C57BL, MESH: Astrocytes, MESH: Morphine, Astrocytes, Neuroscience, 030217 neurology & neurosurgery
Abstract: Endogenous morphine, morphine-6-glucuronide, and codeine, which are structurally identical to vegetal alkaloids, can be synthesized by mammalian cells from dopamine. However, the role of brain endogenous morphine and its derivative compounds is a matter of debate, and knowledge about its distribution is lacking. In this study, by using a validated antibody, we describe a precise mapping of endogenous morphine-like compounds (morphine and/or its glucuronides and/or codeine) in the mouse brain. First, a mass spectrometry approach confirmed the presence of morphine and codeine in mouse brain, but also, of morphine-6-glucuronide and morphine-3-glucuronide representing two metabolites of morphine. Second, light microscopy allowed us to observe immunopositive cell somas and cytoplasmic processes throughout the mouse brain. Morphine-like immunoreactivity was present in various structures including the hippocampus, olfactory bulb, band of Broca, basal ganglia, and cerebellum. Third, by using confocal microscopy and immunofluroscence co-localization, we characterized cell types containing endogenous opiates. Interestingly, we observed that morphine-like immunoreactivity throughout the encephalon is mainly present in γ-aminobutyric acid (GABA)ergic neurons. Astrocytes were also labeled throughout the entire brain, in the cell body, in the cytoplasmic processes, and in astrocytic feet surrounding blood vessels. Finally, ultrastructural localization of morphine-like immunoreactivity was determined by electron microscopy and showed the presence of morphine-like label in presynaptic terminals in the cerebellum and postsynaptic terminals in the rest of the mouse brain. In conclusion, the presence of endogenous morphine-like compounds in brain regions not usually involved in pain modulation opens the exciting opportunity to extend the role and function of endogenous alkaloids far beyond their analgesic functions. J. Comp. Neurol. 519:2390–2416, 2011. © 2011 Wiley-Liss, Inc.
Published: 2011

13. Endogenous morphine-like compound immunoreactivity increases in parkinsonism

Author: Alain Van Dorsselaer, Yannick Goumon, Amandine Berthet, Alexis Laux, Qin Li, Pedro Barroso-Chinea, G. Charron, Evelyne Doudnikoff, Chuan Qin, Erwan Bezard, Marika Nosten-Bertrand, Gregory Porras, Marie-Hélène Canron, Bruno Giros, Anne Vital, François Delalande, Institut des Maladies Neurodégénératives [Bordeaux] (IMN), Université de Bordeaux (UB)-Centre National de la Recherche Scientifique (CNRS), Physiopathologie du système nerveux., Université Louis Pasteur - Strasbourg I-IFR37-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut des Neurosciences Cellulaires et Intégratives (INCI), Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS), Laboratoire des signaux et systèmes (L2S), Université Paris-Sud - Paris 11 (UP11)-CentraleSupélec-Centre National de la Recherche Scientifique (CNRS), Motac Neuroscience, Manchester, United Kingdom., Motac Neuroscience, Institute of Laboratory Animal Sciences, China Academy of Medical Sciences, Department of Laboratory Animal Sciences, Capital Medical University, Beijing-Capital Medical University, Beijing, Institute of Lab Animal Sciences, China Academy of Medical Sciences, Neurobiologie et Psychiatrie, Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université Pierre et Marie Curie - Paris 6 (UPMC), Physiopathologie des Maladies du Système Nerveux Central, 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), Equipe Direction scientifique, Sciences et Technologies de la Musique et du Son (STMS), Institut de Recherche et Coordination Acoustique/Musique (IRCAM)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche et Coordination Acoustique/Musique (IRCAM)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS), Laboratoire de Spectrométrie de Masse BioOrganique [Strasbourg] (LSMBO), Département Sciences Analytiques et Interactions Ioniques et Biomoléculaires (DSA-IPHC), Institut Pluridisciplinaire Hubert Curien (IPHC), Université de Strasbourg (UNISTRA)-Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA))-Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)-Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA))-Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Centre National de la Recherche Scientifique (CNRS)-Institut Pluridisciplinaire Hubert Curien (IPHC), Université de Strasbourg (UNISTRA)-Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA))-Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)-Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA))-Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Centre National de la Recherche Scientifique (CNRS), Centre de Recherche sur la Matière Divisée (CRMD), Université d'Orléans (UO)-Centre National de la Recherche Scientifique (CNRS), Département Neurotransmission et sécrétion neuroendocrine, Centre National de la Recherche Scientifique (CNRS), Université de Strasbourg (UNISTRA)-Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)-Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Centre National de la Recherche Scientifique (CNRS)-Institut Pluridisciplinaire Hubert Curien (IPHC), Université de Strasbourg (UNISTRA)-Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)-Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Centre National de la Recherche Scientifique (CNRS), Centre National de la Recherche Scientifique (CNRS)-Université d'Orléans (UO), and GUERIN, Chantal
Subjects: Male, Dopamine, [SDV]Life Sciences [q-bio], Dopamine Agents, Endogeny, Functional Laterality, Levodopa, Rats, Sprague-Dawley, Mice, chemistry.chemical_compound, 0302 clinical medicine, Tandem Mass Spectrometry, Enzyme Inhibitors, Organic Chemicals, Microscopy, Immunoelectron, Chromatography, High Pressure Liquid, 0303 health sciences, Glutamate Decarboxylase, Parkinsonism, S100 Proteins, Brain, Middle Aged, 3. Good health, [SDV] Life Sciences [q-bio], medicine.anatomical_structure, 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine, Female, Oxidopamine, medicine.drug, Dopamine and cAMP-Regulated Phosphoprotein 32, medicine.medical_specialty, Central nervous system, Enzyme-Linked Immunosorbent Assay, Mice, Transgenic, S100 Calcium Binding Protein beta Subunit, Medium spiny neuron, Choline O-Acetyltransferase, 03 medical and health sciences, Parkinsonian Disorders, Internal medicine, Glial Fibrillary Acidic Protein, medicine, Animals, Humans, Nerve Growth Factors, Aged, 030304 developmental biology, Analysis of Variance, Dopamine Plasma Membrane Transport Proteins, Receptors, Dopamine D2, business.industry, Medial Forebrain Bundle, Dendrites, medicine.disease, Rats, nervous system diseases, Mice, Inbred C57BL, Disease Models, Animal, Macaca fascicularis, alpha-Methyltyrosine, Endocrinology, Gene Expression Regulation, chemistry, Postmortem Changes, Alpha-Methyltyrosine, Neurology (clinical), business, 030217 neurology & neurosurgery
Abstract: International audience; Morphine is endogenously synthesized in the central nervous system and endogenous dopamine is thought to be necessary for endogenous morphine formation. As Parkinson's disease results from the loss of dopamine and is associated with central pain, we considered how endogenous morphine is regulated in the untreated and l-DOPA-treated parkinsonian brain. However, as the cellular origin and overall distribution of endogenous morphine remains obscure in the pathological adult brain, we first characterized the distribution of endogenous morphine-like compound immunoreactive cells in the rat striatum. We then studied changes in the endogenous morphine-like compound immunoreactivity of medium spiny neurons in normal, Parkinson's disease-like and l-DOPA-treated Parkinson's disease-like conditions in experimental (rat and monkey) and human Parkinson's disease. Our results reveal an unexpected dramatic upregulation of neuronal endogenous morphine-like compound immunoreactivity and levels in experimental and human Parkinson's disease, only partially normalized by l-DOPA treatment. Our data suggest that endogenous morphine formation is more complex than originally proposed and that the parkinsonian brain experiences a dramatic upregulation of endogenous morphine immunoreactivity. The functional consequences of such endogenous morphine upregulation are as yet unknown, but based upon the current knowledge of morphine signalling, we hypothesize that it is involved in fatigue, depression and pain symptoms experienced by patients with Parkinson's disease.
Published: 2011

14. Detection of prion protein in urine-derived injectable fertility products by a targeted proteomic approach

Author: Christine Carapito, François Delalande, Daniel Krewski, Alain Van Dorsselaer, Hélène Diemer, Douglas S. McNair, Neil R. Cashman, Christine Schaeffer-Reiss, and Danièle Thiersé
Subjects: Proteomics, Bacterial Diseases, Anatomy and Physiology, Nosocomial Infections, Physiology, Urine, Chorionic Gonadotropin, Mass Spectrometry, Human chorionic gonadotropin, 0302 clinical medicine, Endocrinology, Electrophoresis, Gel, Two-Dimensional, 0303 health sciences, education.field_of_study, 030219 obstetrics & reproductive medicine, Multidisciplinary, Obstetrics and Gynecology, Reference Standards, 3. Good health, Medicine, Infectious diseases, Female, Menotropins, Gonadotropin, Research Article, Infertility, endocrine system, Drugs and Devices, Prion diseases, medicine.drug_class, Prions, Urinary system, Science, Population, Molecular Sequence Data, Endocrine System, Biology, Incubation period, Fertility Agents, Injections, 03 medical and health sciences, Adverse Reactions, medicine, Humans, Reproductive Endocrinology, Amino Acid Sequence, education, 030304 developmental biology, Endocrine Physiology, medicine.disease, Female Subfertility, Hormones, Creutzfeldt-Jakob disease, nervous system diseases, Immunology, Peptides, Chromatography, Liquid
Abstract: BackgroundIatrogenic transmission of human prion disease can occur through medical or surgical procedures, including injection of hormones such as gonadotropins extracted from cadaver pituitaries. Annually, more than 300,000 women in the United States and Canada are prescribed urine-derived gonadotropins for infertility. Although menopausal urine donors are screened for symptomatic neurological disease, incubation of Creutzfeldt-Jakob disease (CJD) is impossible to exclude by non-invasive testing. Risk of carrier status of variant CJD (vCJD), a disease associated with decades-long peripheral incubation, is estimated to be on the order of 100 per million population in the United Kingdom. Studies showing infectious prions in the urine of experimental animals with and without renal disease suggest that prions could be present in asymptomatic urine donors. Several human fertility products are derived from donated urine; recently prion protein has been detected in preparations of human menopausal gonadotropin (hMG).Methodology/principal findingsUsing a classical proteomic approach, 33 and 34 non-gonadotropin proteins were identified in urinary human chorionic gonadotropin (u-hCG) and highly-purified urinary human menopausal gonadotropin (hMG-HP) products, respectively. Prion protein was identified as a major contaminant in u-hCG preparations for the first time. An advanced prion protein targeted proteomic approach was subsequently used to conduct a survey of gonadotropin products; this approach detected human prion protein peptides in urine-derived injectable fertility products containing hCG, hMG and hMG-HP, but not in recombinant products.Conclusions/significanceThe presence of protease-sensitive prion protein in urinary-derived injectable fertility products containing hCG, hMG, and hMG-HP suggests that prions may co-purify in these products. Intramuscular injection is a relatively efficient route of transmission of human prion disease, and young women exposed to prions can be expected to survive an incubation period associated with a minimal inoculum. The risks of urine-derived fertility products could now outweigh their benefits, particularly considering the availability of recombinant products.
Published: 2010

15. Endogenous Morphine Levels Are Increased in Sepsis: A Partial Implication of Neutrophils

Author: Benoît-Joseph Laventie, Marie-Hélène Metz-Boutigue, Thomas Lavaux, Yannick Goumon, Elise Glattard, Alain Van Dorsselaer, Didier A. Colin, Ingeborg Welters, Alexis Laux, Sylvie Dirrig-Grosch, Arnaud Muller, Alexander R. Schmidt, Francis Schneider, Dan-Dan Zhang, François Delalande, Dominique Aunis, Physiopathologie du système nerveux., Université Louis Pasteur - Strasbourg I-IFR37-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut des Neurosciences Cellulaires et Intégratives (INCI), Université Louis Pasteur - Strasbourg I-Centre National de la Recherche Scientifique (CNRS), University of Liverpool, Universitatsklinikum Giessen und Marburg [Marburg,Germany], Service de Réanimation Médicale [Strasbourg], Les Hôpitaux Universitaires de Strasbourg (HUS), Physiopathologie des arthrites, Université Louis Pasteur - Strasbourg I, Institut Pluridisciplinaire Hubert Curien (IPHC), Université de Strasbourg (UNISTRA)-Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Centre National de la Recherche Scientifique (CNRS), Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS), and Goumon, Yannick
Subjects: Lipopolysaccharides, Neutrophils, Receptors, Opioid, mu, lcsh:Medicine, Endogeny, MESH: Flow Cytometry, Pharmacology, MESH: Neutrophils, Lymphocyte Activation, Biochemistry, [SCCO]Cognitive science, Critical Care and Emergency Medicine/Sepsis and Multiple Organ Failure, Tandem Mass Spectrometry, MESH: Microscopy, Confocal, lcsh:Science, MESH: Sepsis, Multidisciplinary, Microscopy, Confocal, medicine.diagnostic_test, Morphine, Chemistry, Alkaloid, MESH: Enzyme-Linked Immunosorbent Assay, Flow Cytometry, Immunohistochemistry, Electrophoresis, Polyacrylamide Gel, medicine.drug, Research Article, Blotting, Western, MESH: Receptors, Opioid, mu, Enzyme-Linked Immunosorbent Assay, Flow cytometry, Sepsis, Immune system, medicine, MESH: Blotting, Western, Humans, Secretion, Interleukin 8, MESH: Lymphocyte Activation, MESH: Humans, lcsh:R, Interleukin-8, MESH: Tandem Mass Spectrometry, MESH: Immunohistochemistry, [SCCO] Cognitive science, Cell Biology, medicine.disease, MESH: Interleukin-8, MESH: Morphine, Immunology, lcsh:Q, MESH: Lipopolysaccharides, MESH: Electrophoresis, Polyacrylamide Gel
Abstract: International audience; Background: Mammalian cells synthesize morphine and the respective biosynthetic pathway has been elucidated. Human neutrophils release this alkaloid into the media after exposure to morphine precursors. However, the exact role of endogenous morphine in inflammatory processes remains unclear. We postulate that morphine is released during infection and can be determined in the serum of patients with severe infection such as sepsis.Methodology: The presence and subcellular immunolocalization of endogenous morphine was investigated by ELISA, mass spectrometry analysis and laser confocal microscopy. Neutrophils were activated with Interleukin-8 (IL-8) or lipopolysaccharide (LPS). Morphine secretion was determined by a morphine-specific ELISA. mu opioid receptor expression was assessed with flow cytometry. Serum morphine concentrations of septic patients were determined with a morphine-specific ELISA and morphine identity was confirmed in human neutrophils and serum of septic patients by mass spectrometry analysis. The effects of the concentration of morphine found in serum of septic patients on LPS-induced release of IL-8 by human neutrophils were tested.Principal findings: We confirmed the presence of morphine in human neutrophil extracts and showed its colocalisation with lactoferrin within the secondary granules of neutrophils. Morphine secretion was quantified in the supernatant of activated human polymorphonuclear neutrophils in the presence and absence of Ca(2+). LPS and IL-8 were able to induce a significant release of morphine only in presence of Ca(2+). LPS treatment increased mu opioid receptor expression on neutrophils. Low concentration of morphine (8 nM) significantly inhibited the release of IL-8 from neutrophils when coincubated with LPS. This effect was reversed by naloxone. Patients with sepsis, severe sepsis and septic shock had significant higher circulating morphine levels compared to patients with systemic inflammatory response syndrome and healthy controls. Mass spectrometry analysis showed that endogenous morphine from serum of patient with sepsis was identical to poppy-derived morphine.Conclusions: Our results indicate that morphine concentrations are increased significantly in the serum of patients with systemic infection and that morphine is, at least in part, secreted from neutrophils during sepsis. Morphine concentrations equivalent to those found in the serum of septic patients significantly inhibited LPS-induced IL-8 secretion in neutrophils.
Published: 2010

16. The thioredoxin-like protein rod-derived cone viability factor (RdCVFL) interacts with TAU and inhibits its phosphorylation in the retina

Author: François Delalande, Olivier Poch, Therese Cronin, Géraldine Millet-Puel, Ram Fridlich, Alain Van Dorsselaer, Arne Holmgren, Céline Jaillard, Jun Lu, Ludivine Perrocheau, Thierry Léveillard, José-Alain Sahel, Marie-Laure Niepon, Laetitia Poidevin, Laboratoire de Physiopathologie Cellulaire et Moleculaire de la Retine, Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut Pluridisciplinaire Hubert Curien (IPHC), Université de Strasbourg (UNISTRA)-Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA))-Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Centre National de la Recherche Scientifique (CNRS), Department of Medical Biochemistry and Biophysics, karolinska institute-Medical Nobel Institute for Biochemistry, 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), 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), Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Université de Strasbourg (UNISTRA)-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 Pierre et Marie Curie - Paris 6 (UPMC), Peney, Maité, and Université de Strasbourg (UNISTRA)-Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Centre National de la Recherche Scientifique (CNRS)
Subjects: Retinal degeneration, MESH: Protein Isoforms, Biochemistry, MESH: Mice, Knockout, Analytical Chemistry, Mice, Thioredoxins, 0302 clinical medicine, MESH: Thioredoxins, MESH: Eye Proteins, Tandem Mass Spectrometry, Protein Isoforms, MESH: Animals, Phosphorylation, Mice, Knockout, Mice, Inbred BALB C, 0303 health sciences, MESH: Oxidative Stress, biology, MESH: Retina, 3. Good health, MESH: tau Proteins, Signal transduction, Thioredoxin, Protein Binding, Programmed cell death, Tau protein, MESH: Mice, Inbred BALB C, tau Proteins, Retina, Cell Line, 03 medical and health sciences, Retinitis pigmentosa, medicine, Animals, Humans, MESH: Protein Binding, Eye Proteins, Molecular Biology, MESH: Mice, 030304 developmental biology, MESH: Humans, MESH: Phosphorylation, Research, Alternative splicing, MESH: Tandem Mass Spectrometry, medicine.disease, Molecular biology, MESH: Cell Line, Oxidative Stress, biology.protein, sense organs, MESH: Chromatography, Liquid, 030217 neurology & neurosurgery, Chromatography, Liquid
Abstract: International audience; Rod-derived cone viability factor (RdCVF) is produced by the Nxnl1 gene that codes for a second polypeptide, RdCVFL, by alternative splicing. Although the role of RdCVF in promoting cone survival has been described, the implication of RdCVFL, a putative thioredoxin enzyme, in the protection of photoreceptors is presently unknown. Using a proteomics approach we identified 90 proteins interacting with RdCVFL including the microtubule-binding protein TAU. We demonstrate that the level of phosphorylation of TAU is increased in the retina of the Nxnl1(-/-) mice as it is hyperphosphorylated in the brain of patients suffering from Alzheimer disease, presumably in some cases through oxidative stress. Using a cell-based assay, we show that RdCVFL inhibits TAU phosphorylation. In vitro, RdCVFL protects TAU from oxidative damage. Photooxidative stress is implicated in retinal degeneration, particularly in retinitis pigmentosa, where it is considered to be a contributor to secondary cone death. The functional interaction between RdCVFL and TAU described here is the first characterization of the RdCVFL signaling pathway involved in neuronal cell death mediated by oxidative stress.
Published: 2009

17. XRCC1 interacts with the p58 subunit of DNA Pol alpha-primase and may coordinate DNA repair and replication during S phase

Author: Josiane M√©nissier-de Murcia, Nicolas Lévy, Alain Van Dorsselaer, Maren Oehlmann, Anne Bresson, Domenico Maiorano, V. Schreiber, François Delalande, Heinz-Peter Nasheuer, Gilbert de Murcia, 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), Institut de recherche de l'Ecole de biotechnologie de Strasbourg (IREBS), National University of Ireland [Galway] (NUI Galway), Laboratoire de Spectrométrie de Masse BioOrganique [Strasbourg] (LSMBO), Département Sciences Analytiques et Interactions Ioniques et Biomoléculaires (DSA-IPHC), Institut Pluridisciplinaire Hubert Curien (IPHC), Université de Strasbourg (UNISTRA)-Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)-Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Centre National de la Recherche Scientifique (CNRS)-Institut Pluridisciplinaire Hubert Curien (IPHC), Université de Strasbourg (UNISTRA)-Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)-Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Centre National de la Recherche Scientifique (CNRS), Institut de génétique humaine (IGH), Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), and Larose, Catherine
Subjects: XRCC1, DNA Repair, DNA polymerase, Poly (ADP-Ribose) Polymerase-1, [SDV.GEN] Life Sciences [q-bio]/Genetics, Genome Integrity, Repair and Replication, DNA polymerase delta, S Phase, polymerase-alpha-primase, Xenopus laevis, 0302 clinical medicine, single strand break repair (SSBR) complex, poly(adp-ribose) polymerase, ComputingMilieux_MISCELLANEOUS, 0303 health sciences, damaged DNA, biology, xenopus egg extracts, Sciences du Vivant [q-bio]/Biotechnologies, Chromatin, DNA-Binding Proteins, 030220 oncology & carcinogenesis, sister-chromatid exchange, Primase, Poly(ADP-ribose) Polymerases, complex, DNA Replication, DNA polymerase II, DNA repair, DNA Primase, DNA replication, [SDV.GEN.GH] Life Sciences [q-bio]/Genetics/Human genetics, 03 medical and health sciences, Control of chromosome duplication, strand break repair, Genetics, Animals, Humans, Protein Interaction Domains and Motifs, Replication protein A, parp-1, 030304 developmental biology, [SDV.GEN]Life Sciences [q-bio]/Genetics, Processivity, DNA, DNA Polymerase I, Molecular biology, proteins, X-ray Repair Cross Complementing Protein 1, cell-cycle, [SDV.GEN.GH]Life Sciences [q-bio]/Genetics/Human genetics, biology.protein, DNA Damage, HeLa Cells
Abstract: Repair of single-stranded DNA breaks before DNA replication is critical in maintaining genomic stability; however, how cells deal with these lesions during S phase is not clear. Using combined approaches of proteomics and in vitro and in vivo protein–protein interaction, we identified the p58 subunit of DNA Pol α-primase as a new binding partner of XRCC1, a key protein of the single strand break repair (SSBR) complex. In vitro experiments reveal that the binding of poly(ADP-ribose) to p58 inhibits primase activity by competition with its DNA binding property. Overexpression of the XRCC1-BRCT1 domain in HeLa cells induces poly(ADP-ribose) synthesis, PARP-1 and XRCC1-BRCT1 poly(ADP-ribosyl)ation and a strong S phase delay in the presence of DNA damage. Addition of recombinant XRCC1-BRCT1 to Xenopus egg extracts slows down DNA synthesis and inhibits the binding of PCNA, but not MCM2 to alkylated chromatin, thus indicating interference with the assembly of functional replication forks. Altogether these results suggest a critical role for XRCC1 in connecting the SSBR machinery with the replication fork to halt DNA synthesis in response to DNA damage. Centre National de la Recherche Scientifique; Association pour la Recherche contre le Cancer; Electricité de France; Ligue contre le Cancer Comité du Bas-Rhin; Commissariat à l’Energie Atomique and Agence Nationale pour la Recherche; Science Foundation Ireland; Health Research Board, Ireland; INTAS (Brussels, Belgium) Deposited by bulk import
Published: 2009

18. Two chromogranin a-derived peptides induce calcium entry in human neutrophils by calmodulin-regulated calcium independent phospholipase A2

Author: Didier A. Colin, Dan-Dan Zhang, Dominique Aunis, Gilles Prévost, Marie-Hélène Metz-Boutigue, Jean de Barry, Sylvette Chasserot-Golaz, Karen B. Helle, Peiman Shooshtarizadeh, Jasmina Vidic, Benoît-Joseph Laventie, Francis Schneider, Alain Van Dorsselaer, François Delalande, Jean-François Chich, Physiopathologie du système nerveux., Université Louis Pasteur - Strasbourg I-IFR37-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre Hospitalier Universitaire de Strasbourg (CHU de Strasbourg ), Chongqing University, Université de Strasbourg (UNISTRA), Unité de recherche Virologie et Immunologie Moléculaires (VIM (UR 0892)), Institut National de la Recherche Agronomique (INRA), Institut des Neurosciences Cellulaires et Intégratives (INCI), Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS), Laboratoire de Spectrométrie de Masse BioOrganique [Strasbourg] (LSMBO), Département Sciences Analytiques et Interactions Ioniques et Biomoléculaires (DSA-IPHC), Institut Pluridisciplinaire Hubert Curien (IPHC), Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS)-Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS)-Institut Pluridisciplinaire Hubert Curien (IPHC), Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS)-Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS), Department of Biomedicine, University of Bergen (UiB), Université de Strasbourg (UNISTRA)-Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)-Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Centre National de la Recherche Scientifique (CNRS)-Institut Pluridisciplinaire Hubert Curien (IPHC), and Université de Strasbourg (UNISTRA)-Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)-Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Centre National de la Recherche Scientifique (CNRS)
Subjects: Proteomics, Calmodulin, Neutrophils, Immunology/Innate Immunity, Antimicrobial peptides, Immunology/Immunomodulation, chemistry.chemical_element, lcsh:Medicine, [SDV.BC]Life Sciences [q-bio]/Cellular Biology, Calcium, Biochemistry, Cell Biology/Cell Signaling, Calcium in biology, Flow cytometry, 03 medical and health sciences, 0302 clinical medicine, Calcium imaging, medicine, Extracellular, Humans, Calcium Signaling, lcsh:Science, Cells, Cultured, 030304 developmental biology, Calcium signaling, 0303 health sciences, Multidisciplinary, Dose-Response Relationship, Drug, biology, medicine.diagnostic_test, lcsh:R, Biochemistry/Chemical Biology of the Cell, Proteins, Cell Biology, Peptide Fragments, chemistry, Phospholipases A2, Calcium-Independent, biology.protein, Chromogranin A, lcsh:Q, 030217 neurology & neurosurgery, Research Article
Abstract: International audience; Background: Antimicrobial peptides derived from the natural processing of chromogranin A (CgA) are co-secreted with catecholamines upon stimulation of chromaffin cells. Since PMNs play a central role in innate immunity, we examine responses by PMNs following stimulation by two antimicrobial CgA-derived peptides. Methodology/Principal Findings: PMNs were treated with different concentrations of CgA-derived peptides in presence of several drugs. Calcium mobilization was observed by using flow cytometry and calcium imaging experiments. Immunocytochemistry and confocal microscopy have shown the intracellular localization of the peptides. The calmodulin-binding and iPLA2 activating properties of the peptides were shown by Surface Plasmon Resonance and iPLA2 activity assays. Finally, a proteomic analysis of the material released after PMNs treatment with CgA-derived peptides was performed by using HPLC and Nano-LC MS-MS. By using flow cytometry we first observed that after 15 s, in presence of extracellular calcium, Chromofungin (CHR) or Catestatin (CAT) induce a concentration-dependent transient increase of intracellular calcium. In contrast, in absence of extra cellular calcium the peptides are unable to induce calcium depletion from the stores after 10 minutes exposure. Treatment with 2-APB (2-aminoethoxydiphenyl borate), a store operated channels (SOCs) blocker, inhibits completely the calcium entry, as shown by calcium imaging. We also showed that they activate iPLA2 as the two CaM-binding factors (W7 and CMZ) and that the two sequences can be aligned with the two CaMbinding domains reported for iPLA2. We finally analyzed by HPLC and Nano-LC MS-MS the material released by PMNs following stimulation by CHR and CAT. We characterized several factors important for inflammation and innate immunity. Conclusions/Significance: For the first time, we demonstrate that CHR and CAT, penetrate into PMNs, inducing extracellular calcium entry by a CaM-regulated iPLA2 pathway. Our study highlights the role of two CgA-derived peptides in the active communication between neuroendocrine and immune systems.
Published: 2009

19. Endogenous Morphine in SH-SY5Y Cells and the Mouse Cerebellum

Author: G. Roussel, Véronique Kemmel, Yannick Goumon, Marie-Hélène Metz-Boutigue, Alain Van Dorsselaer, Elise Glattard, Omar Taleb, Alexis Laux, Monique Miehe, Arnaud Muller, François Delalande, Dominique Aunis, Physiopathologie du système nerveux., Université Louis Pasteur - Strasbourg I-IFR37-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut de Chimie Biologique [Strasbourg] (ICB), Institut Pluridisciplinaire Hubert Curien (IPHC), Université Louis Pasteur - Strasbourg I-Centre National de la Recherche Scientifique (CNRS), École Européene de Chimie, Polymères et Matériaux de Strasbourg (ECPM), Université de Strasbourg (UNISTRA), Laboratoire de Spectrométrie de Masse BioOrganique [Strasbourg] (LSMBO), Département Sciences Analytiques et Interactions Ioniques et Biomoléculaires (DSA-IPHC), Université de Strasbourg (UNISTRA)-Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)-Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Centre National de la Recherche Scientifique (CNRS)-Institut Pluridisciplinaire Hubert Curien (IPHC), Université de Strasbourg (UNISTRA)-Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)-Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Centre National de la Recherche Scientifique (CNRS), Institut des Neurosciences Cellulaires et Intégratives (INCI), Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS), and Goumon, Yannick
Subjects: Cerebellum, SH-SY5Y, Physiology, Purkinje cell, lcsh:Medicine, Pharmacology, MESH: Glucuronosyltransferase, Biochemistry, Synaptic Transmission, [SCCO]Cognitive science, Mice, Neuroblastoma, Purkinje Cells, MESH: Animals, MESH: Brain Chemistry, Glucuronosyltransferase, lcsh:Science, MESH: Electrophysiology, Multidisciplinary, Morphine, Neuroscience/Neuronal and Glial Cell Biology, Cell biology, Electrophysiology, medicine.anatomical_structure, MESH: Morphine Derivatives, Research Article, Cell type, MESH: Cell Line, Tumor, Central nervous system, Biology, MESH: Purkinje Cells, Alkaloids, MESH: Alkaloids, Basket cell, Cell Line, Tumor, MESH: Synaptic Transmission, medicine, Animals, Humans, MESH: Mice, Brain Chemistry, Morphine Derivatives, MESH: Humans, lcsh:R, [SCCO] Cognitive science, Cell Biology, MESH: Neuroblastoma, MESH: Cerebellum, Olfactory bulb, MESH: Morphine, Chromaffin cell, Cell Biology/Neuronal and Glial Cell Biology, lcsh:Q, Neuroscience
Abstract: International audience; Background: Morphine, the principal active agent in opium, is not restricted to plants, but is also present in different animal tissues and cell types, including the mammalian brain. In fact, its biosynthetic pathway has been elucidated in a human neural cell line. These data suggest a role for morphine in brain physiology (e.g., neurotransmission), but this hypothesis remains a matter of debate. Recently, using the adrenal neuroendocrine chromaffin cell model, we have shown the presence of morphine-6-glucuronide (M6G) in secretory granules and their secretion products, leading us to propose that these endogenous alkaloids might represent new neuroendocrine factors. Here, we investigate the potential function of endogenous alkaloids in the central nervous system.Methodology and principal findings: Microscopy, molecular biology, electrophysiology, and proteomic tools were applied to human neuroblastoma SH-SY5Y cells (i) to characterize morphine and M6G, and (ii) to demonstrate the presence of the UDP-glucuronyltransferase 2B7 enzyme, which is responsible for the formation of M6G from morphine. We show that morphine is secreted in response to nicotine stimulation via a Ca(2+)-dependent mechanism involving specific storage and release mechanisms. We also show that morphine and M6G at concentrations as low as 10(-10) M are able to evoke specific naloxone-reversible membrane currents, indicating possible autocrine/paracrine regulation in SH-SY5Y cells. Microscopy and proteomic approaches were employed to detect and quantify endogenous morphine in the mouse brain. Morphine is present in the hippocampus, cortex, olfactory bulb, and cerebellum at concentration ranging from 1.45 to 7.5 pmol/g. In the cerebellum, morphine immunoreactivity is localized to GABA basket cells and their termini, which form close contacts on Purkinje cell bodies.Conclusions/significance: The presence of morphine in the brain and its localization in particular areas lead us to conclude that it has a specific function in neuromodulation and/or neurotransmission. Furthermore, its presence in cerebellar basket cell termini suggests that morphine has signaling functions in Purkinje cells that remain to be discovered.
Published: 2008

20. Proteomic analysis of brain tissue from an Alzheimer's disease mouse model by two-dimensional difference gel electrophoresis

Author: Anthony A. High, François Delalande, Parker Fabienne, Daria Sizova, Florence Poirier, Anita Diu-Hercend, Duchesne Marc, Alain Van Dorsselaer, and Elodie Charbaut
Subjects: Genetically modified mouse, Diagnostic Imaging, Male, Proteomics, Aging, Transgene, Blotting, Western, Mice, Transgenic, Biology, Amyloid beta-Protein Precursor, Mice, Apolipoproteins E, Alzheimer Disease, Glial Fibrillary Acidic Protein, medicine, Animals, Humans, Electrophoresis, Gel, Two-Dimensional, Pathological, Two-Dimensional Difference Gel Electrophoresis, Two-dimensional gel electrophoresis, General Neuroscience, Neurodegeneration, Wild type, Brain, medicine.disease, Molecular biology, Mice, Inbred C57BL, Disease Models, Animal, Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization, Female, Neurology (clinical), Geriatrics and Gerontology, Developmental Biology
Abstract: We used a beta-amyloid precursor protein (APP) transgenic (Tg) mouse model that displays some of the typical Alzheimer-associated pathological features to study the brain proteoma associated with amyloid plaque deposition. Two groups (male and female) of 14-month-old Tg mice were compared with their wild type littermates. We used differential 2D electrophoresis coupled with mass spectrometry to generate one of the first complete image of changes in brain protein expression occurring in this well-recognized model of Alzheimer's disease (AD). We identified 15 different proteins, which are significantly regulated in this pathology (p0.05,or =1.5-fold variation in expression comparing with the wild type samples). These comprise a number of proteins that were already known to be implicated in AD and neurodegeneration, as well as several proteins which relationship with AD had not been shown before. Identified proteins were grouped according to their biological key pathways. Results obtained are discussed in view of existing bibliographic data on human AD transcriptoma and proteoma.
Published: 2005

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20 results on '"François Delalande"'

1. Combining label-free and label-based accurate quantifications with SWATH-MS: Comparison with SRM and PRM for the evaluation of bovine muscle type effects

2. Ral GTPases promote breast cancer metastasis by controlling biogenesis and organ targeting of exosomes

3. Zika virus enhances monocyte adhesion and transmigration favoring viral dissemination to neural cells

4. Post-Translational Regulation of the Glucose-6-Phosphatase Complex by Cyclic Adenosine Monophosphate Is a Crucial Determinant of Endogenous Glucose Production and Is Controlled by the Glucose-6-Phosphate Transporter

5. The ESCRT-III Protein CHMP1A Mediates Secretion of Sonic Hedgehog on a Distinctive Subtype of Extracellular Vesicles

6. Validating Missing Proteins in Human Sperm Cells by Targeted Mass-Spectrometry- and Antibody-based Methods

7. FACTORS INFLUENCING REIMBURSEMENT OF MEDICAL DEVICES IN FRANCE

8. A ruthenium anticancer compound interacts with histones and impacts differently on epigenetic and death pathways compared to cisplatin

9. Cdx2 homeoprotein inhibits non-homologous end joining in colon cancer but not in leukemia cells

10. Differentiation between fresh and frozen–thawed sea bass (Dicentrarchus labrax) fillets using two-dimensional gel electrophoresis

11. Rod-derived cone viability factor promotes cone survival by stimulating aerobic glycolysis

12. Mapping of endogenous morphine-like compounds in the adult mouse brain: Evidence of their localization in astrocytes and GABAergic cells

13. Endogenous morphine-like compound immunoreactivity increases in parkinsonism

14. Detection of prion protein in urine-derived injectable fertility products by a targeted proteomic approach

15. Endogenous Morphine Levels Are Increased in Sepsis: A Partial Implication of Neutrophils

16. The thioredoxin-like protein rod-derived cone viability factor (RdCVFL) interacts with TAU and inhibits its phosphorylation in the retina

17. XRCC1 interacts with the p58 subunit of DNA Pol alpha-primase and may coordinate DNA repair and replication during S phase

18. Two chromogranin a-derived peptides induce calcium entry in human neutrophils by calmodulin-regulated calcium independent phospholipase A2

19. Endogenous Morphine in SH-SY5Y Cells and the Mouse Cerebellum

20. Proteomic analysis of brain tissue from an Alzheimer's disease mouse model by two-dimensional difference gel electrophoresis

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