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18 results on '"MESH: Tissue Culture Techniques"'

1. Rab11a Is Essential for Lamellar Body Biogenesis in the Human Epidermis

Author

Elise Gaspard, Sophie Allart, Michel Simon, Corinne Leprince, Guy Serre, Marie Reynier, Alain Moga, Dominique Goudounèche, Unité différenciation épidermique et auto-immunité rhumatoïde (UDEAR), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut National de la Santé et de la Recherche Médicale (INSERM), SYNELVIA, Centre de Microscopie Électronique Appliquée à la Biologie (CMEAB), Hôpital de Rangueil, CHU Toulouse [Toulouse]-CHU Toulouse [Toulouse]-Toulouse Réseau Imagerie-Genotoul ( TRI-Genotoul), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Toulouse Réseau Imagerie-Genotoul ( TRI-Genotoul), and CARBILLET, Véronique

Subjects
Keratinocytes, 0301 basic medicine, MESH: Organelle Biogenesis, Dermatology, MESH: Homeostasis / genetics, MESH: Keratinocytes / cytology, Lamellar granule, Biology, Biochemistry, Sampling Studies, Tissue Culture Techniques, 03 medical and health sciences, 0302 clinical medicine, MESH: Sampling Studies, MESH: rab GTP-Binding Proteins / genetics, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, medicine, Stratum corneum, Homeostasis, Humans, MESH: Gene Silencing, Lamellar structure, MESH: Tissue Culture Techniques, Gene Silencing, Molecular Biology, Cells, Cultured, Transepidermal water loss, MESH: Humans, Organelle Biogenesis, Corneocyte, integumentary system, Cell Biology, MESH: Epidermis / metabolism, Cell biology, 030104 developmental biology, medicine.anatomical_structure, rab GTP-Binding Proteins, 030220 oncology & carcinogenesis, [SDV.MHEP.MI] Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Organelle biogenesis, Epidermis, Biogenesis, MESH: Cells, Cultured
Abstract

International audience; Most of the skin barrier function is attributable to the outermost layer of the epidermis, the stratum corneum, which is composed of flattened, anucleated cells called corneocytes surrounded by a lipid-enriched lamellar matrix. The composition of the stratum corneum is directly dependent on the underlying granular keratinocytes, which are the last living cells in the stratified epidermis. Many components present in the intercorneocyte matrix are delivered by the underlying granular keratinocytes through a secretion process dependent on lysosome-related organelles called lamellar bodies. Because of the importance of lamellar bodies in the maintenance of the epidermal barrier, the mechanisms regulating their biogenesis must be better understood. In this study, we show that the Rab11a GTPase is highly expressed in terminally differentiated keratinocytes, where it is partly associated with lamellar bodies. Rab11a silencing in three-dimensional in vitro reconstructed human epidermis induces a barrier defect, a decrease in the amount of lipid found in the stratum corneum, a reduction in lamellar body density and secretion areas in granular keratinocytes, and the mis-sorting of lamellar body cargoes being driven to the lysosomal degradation pathway. Our results highlight the importance of Rab11a-dependent regulation of lamellar body biogenesis in keratinocytes and consequently on epidermal barrier homeostasis.

Published
2016

2. Human testis steroidogenesis is inhibited by phthalates

Author

Océane Albert, Francois Guille, Frédérique Courant, Laurianne Lesné, Elisabeth Perdu, B. Le Bizec, Christèle Desdoits-Lethimonier, Daniel Zalko, Nathalie Dejucq-Rainsford, Bernard Jégou, Jégou, Bernard, Environnement viral et chimique & reproduction, Institut de recherche en santé, environnement et travail (Irset), 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 )-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 ), Laboratoire d'étude des Résidus et Contaminants dans les Aliments (LABERCA), Institut National de la Recherche Agronomique (INRA)-Ecole Nationale Vétérinaire, Agroalimentaire et de l'alimentation Nantes-Atlantique (ONIRIS), ToxAlim (ToxAlim), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Ecole Nationale Vétérinaire de Toulouse (ENVT), Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Ecole d'Ingénieurs de Purpan (INPT - EI Purpan), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Recherche Agronomique (INRA), CRLCC Eugène Marquis (CRLCC), Métabolisme et Xénobiotiques (ToxAlim-MeX), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Recherche Agronomique (INRA)-Université Toulouse III - Paul Sabatier (UT3), 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 )-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 ), Institut National de la Recherche Agronomique (INRA)-École nationale vétérinaire, agroalimentaire et de l'alimentation Nantes-Atlantique (ONIRIS), Institut National de la Recherche Agronomique (INRA)-Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université de Toulouse (UT)-Ecole Nationale Vétérinaire de Toulouse (ENVT), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National Polytechnique (Toulouse) (Toulouse INP), Université de Toulouse (UT)-Ecole d'Ingénieurs de Purpan (INP - PURPAN), Université de Toulouse (UT)-Université de Toulouse (UT), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National de la Recherche Agronomique (INRA)-Université Toulouse III - Paul Sabatier (UT3), Le Corre, Morgane, Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Ecole Nationale Vétérinaire de Toulouse (ENVT), Université Fédérale Toulouse Midi-Pyrénées-Ecole d'Ingénieurs de Purpan (INPT - EI Purpan), and Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées

Subjects
Male, MESH: Leydig Cells, Apoptosis, 010501 environmental sciences, Testicle, 01 natural sciences, Tissue Culture Techniques, chemistry.chemical_compound, Phthalates, Testis, Insulin, Testosterone, MESH: Proteins, 0303 health sciences, MESH: Testis, Rehabilitation, MESH: Spermatozoa, Phthalate, Leydig Cells, Obstetrics and Gynecology, Sertoli cell, Spermatozoa, 3. Good health, Ketoconazole, medicine.anatomical_structure, Endocrine disruptor, Germ cell, medicine.medical_specialty, endocrine system, medicine.drug_class, Endocrine disruption, MESH: Testosterone, MESH: Insulin, Biology, Cell Line, Andrology, 03 medical and health sciences, MESH: Sertoli Cells, Diethylhexyl Phthalate, Internal medicine, MESH: Diethylhexyl Phthalate, medicine, Humans, Inhibins, MESH: Tissue Culture Techniques, [SDV.BDLR] Life Sciences [q-bio]/Reproductive Biology, 030304 developmental biology, 0105 earth and related environmental sciences, Sertoli Cells, MESH: Humans, MESH: Apoptosis, Proteins, [SDV.BDLR]Life Sciences [q-bio]/Reproductive Biology, MESH: Inhibins, Androgen, MESH: Male, MESH: Cell Line, Endocrinology, MESH: Ketoconazole, Reproductive Medicine, chemistry, Steroidogenesis, human testis, testosterone, phthalates, endocrine disruption, steroidogenesis, [SDV.SPEE] Life Sciences [q-bio]/Santé publique et épidémiologie, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, Human testis
Abstract

International audience; BACKGROUND: Phthalic acid esters are widely used in the manufacture of plastics. Numerous studies have shown that these phthalates impair testicular testosterone production in the rat. However, the scarce and contradictory data concerning humans have cast doubt over whether these compounds are also anti-androgenic in man. We therefore investigated the direct effects of di-(2-ethylhexyl) phthalate (DEHP) and mono-(2-ethylhexyl) phthalate (MEHP) on organo-cultured adult human testis and a human cell line. METHODS: Adult human testis explants or NCI-H295R adrenocortical human cells were cultured with DEHP or MEHP. The effects of ketoconazole, used as a reference molecule, were also assessed. RESULTS: In both models, DEHP and MEHP significantly inhibited testosterone production. The effects of both phthalates appeared to be specific for steroidogenesis, as INSL3 production by Leydig cells was not altered. Furthermore, the phthalates of interest had no effect on inhibin B production by Sertoli cells or on germ cell apoptosis. As only a small fraction of the phthalates added was found in the testis explants, and as these compounds were found to be metabolized, we estimate that the anti-androgenic effects observed occurred at concentrations of phthalates that are of the same order of magnitude as exposures reported in the literature for men. CONCLUSIONS: We provide the first evidence that DEHP and MEHP can inhibit testosterone production in the adult human testis. This is consistent with recent epidemiological findings of an inverse correlation between exposure to MEHP and testosterone concentrations.

Published
2012
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3. Hordeins are expressed in microspore-derived embryos and also during male gametophytic and very early stages of seed development

Author

Amada Pulido, Adela Olmedilla, Beáta Barnabás, Alberto Hernando, Martine Devic, Ferenc Bakos, Enrique Méndez, Laboratoire Génome et développement des plantes (LGDP), and Université de Perpignan Via Domitia (UPVD)-Centre National de la Recherche Scientifique (CNRS)

Subjects
0106 biological sciences, Glutens, Physiology, Blotting, Western, Stamen, Enzyme-Linked Immunosorbent Assay, Plant Science, Biology, 01 natural sciences, Endosperm, [SDV.GEN.GPL]Life Sciences [q-bio]/Genetics/Plants genetics, Tissue Culture Techniques, 03 medical and health sciences, MESH: In Situ Hybridization, Microspore, MESH: Reverse Transcriptase Polymerase Chain Reaction, Botany, MESH: Blotting, Western, MESH: Tissue Culture Techniques, RNA, Messenger, In Situ Hybridization, MESH: RNA, Messenger, Plant Proteins, 030304 developmental biology, 0303 health sciences, MESH: Plant Proteins, Reverse Transcriptase Polymerase Chain Reaction, Embryogenesis, MESH: Enzyme-Linked Immunosorbent Assay, food and beverages, MESH: Immunohistochemistry, Hordeum, Embryo, Immunohistochemistry, Cell biology, MESH: Seeds, Protein body, Hordein, MESH: Hordeum, MESH: Pollen, Seeds, Pollen, Hordeum vulgare, Prolamins, 010606 plant biology & botany
Abstract

Microspore-derived embryos induced by anther or isolated-microspore culture display certain characteristics of zygotic embryos. Furthermore, the expression of certain endosperm genes has been described in these non-zygotic embryos. The expression of hordein genes encoding the main barley endosperm proteins has been studied using a wide range of methods (RT-PCR, in situ hybridization, ELISA sandwich, western blotting immunocytochemistry, and cytochemistry) to ascertain their presence or absence during the induction and first stages of microspore embryogenesis. Due to the very sensitive techniques used it was possible to detect for the first time hordein expression during microspore embryogenesis. Surprisingly, these hordeins were also detected at different stages of male gametophytic development as well as during the very early stages of seed development, when they have not hitherto been detected. The expression and localization of these storage proteins and their corresponding transcripts provide new information about barley microspore embryogenesis and its relationship to zygotic embryogenesis. Although only small quantities of hordeins are accumulated during microspore embryogenesis they seem to be necessary for the initial development of the microspore-derived embryo. This idea is supported by the changes detected in their concentration throughout this process and is in accordance with previously published data concerning the importance of endosperm proteins for embryo development in both microspore culture and in planta.

Published
2006

4. BDNF-TrkB signaling through Erk1/2MAPK phosphorylation mediates the enhancement of fear memory induced by glucocorticoids

Author

P.V. Piazza, Françoise Rougé-Pont, A. Y. Le Roux, N Kaouane, J-M Revest, Aline Desmedt, Monique Vallée, Valérie Roullot-Lacarrière, F Tronche, Fernando Kasanetz, Mines Nantes (Mines Nantes), UMR 5228, Centre National de la Recherche Scientifique (CNRS), Institut de Physique du Globe de Paris (IPGP), Institut national des sciences de l'Univers (INSU - CNRS)-IPG PARIS-Université Paris Diderot - Paris 7 (UPD7)-Université de La Réunion (UR)-Centre National de la Recherche Scientifique (CNRS), Physiopathologie du système nerveux central - Institut François Magendie, Université Bordeaux Segalen - Bordeaux 2-IFR8-Institut National de la Santé et de la Recherche Médicale (INSERM), Génétique moléculaire, neurophysiologie et comportement, Expression des Gènes et comportement adaptatifs = Molecular Genetics, Neurophysiology and Behavior (NPS-15), Neuroscience Paris Seine (NPS), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut de Biologie Paris Seine (IBPS), 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)-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)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut de Biologie Paris Seine (IBPS), 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)-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)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), INSERM, Agence Nationale pour la Recherche (ANR), Federation Bordeaux Neurosciences (FBN), University Victor Segalen-Bordeaux2, Conseil Regional d'Aquitaine, Neurosciences Paris Seine (NPS), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut de Biologie Paris Seine (IBPS), 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)-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)-Centre National de la Recherche Scientifique (CNRS)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut de Biologie Paris Seine (IBPS), 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)-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)-Centre National de la Recherche Scientifique (CNRS), INSERM, Neurocentre Magendie, U1215, Physiopathologie de la Plasticité Neuronale, F-33000 Bordeaux, France, and Centre National de la Recherche Scientifique (CNRS)-Université de La Réunion (UR)-Université Paris Diderot - Paris 7 (UPD7)-IPG PARIS-Institut national des sciences de l'Univers (INSU - CNRS)

Subjects
Male, MESH: Hippocampus, MESH: Receptors, Glucocorticoid, [SDV]Life Sciences [q-bio], MESH: Fear, Hippocampus, MESH: Rats, Sprague-Dawley, Tropomyosin receptor kinase B, MESH: Brain-Derived Neurotrophic Factor, Rats, Sprague-Dawley, Tissue Culture Techniques, 0302 clinical medicine, Glucocorticoid receptor, MESH: Tissue Plasminogen Activator, MESH: Animals, MESH: Memory, Phosphorylation, Receptor, ComputingMilieux_MISCELLANEOUS, 0303 health sciences, tissue plasminogen activator, contextual fear memory, glucocorticoids, MESH: Receptor, trkB, brain-derived neurotrophic factor, MESH: Stress, Psychological, Fear, Psychiatry and Mental health, Original Article, [SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], Signal transduction, Psychology, MESH: Mice, Transgenic, MAP Kinase Signaling System, Transgene, Mice, Transgenic, 03 medical and health sciences, Cellular and Molecular Neuroscience, Receptors, Glucocorticoid, MESH: Mice, Inbred C57BL, Memory, Animals, Receptor, trkB, MESH: Tissue Culture Techniques, tropomyosin-related kinase B, Molecular Biology, extracellular signal-regulated kinases 1/2 mitogen-activated protein kinase, 030304 developmental biology, Brain-derived neurotrophic factor, MESH: Phosphorylation, MESH: MAP Kinase Signaling System, [SCCO.NEUR]Cognitive science/Neuroscience, MESH: Male, Mice, Inbred C57BL, Neuroscience, Stress, Psychological, 030217 neurology & neurosurgery
Abstract

International audience; Activation of glucocorticoid receptors (GR) by glucocorticoid hormones (GC) enhances contextual fear memories through the activation of the Erk1/2(MAPK) signaling pathway. However, the molecular mechanism mediating this effect of GC remains unknown. Here we used complementary molecular and behavioral approaches in mice and rats and in genetically modified mice in which the GR was conditionally deleted (GR(NesCre)). We identified the tPA-BDNF-TrkB signaling pathway as the upstream molecular effectors of GR-mediated phosphorylation of Erk1/2(MAPK) responsible for the enhancement of contextual fear memory. These findings complete our knowledge of the molecular cascade through which GC enhance contextual fear memory and highlight the role of tPA-BDNF-TrkB-Erk1/2(MAPK) signaling pathways as one of the core effectors of stress-related effects of GC.

Published
2014

5. Gliotransmission and Brain Glucose Sensing: Critical Role of Endozepines

Author

Lanfray, Damien, Arthaud, Sébastien, Ouellet, Johanne, Compère, Vincent, Do Rego, Jean-Luc, Leprince, Jérôme, Lefranc, Benjamin, Castel, Hélène, Bouchard, Cynthia, Monge-Roffarello, Boris, Richard, Denis, Pelletier, Georges, Vaudry, Hubert, Tonon, Marie-Christine, Morin, Fabrice, Compere, V., Tonon, C., Différenciation et communication neuronale et neuroendocrine (DC2N), Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Plate-Forme de Recherche en Imagerie Cellulaire de Haute-Normandie (PRIMACEN), Normandie Université (NU)-Normandie Université (NU)-Institute for Research and Innovation in Biomedicine (IRIB), Normandie Université (NU)-Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut Fédératif de Recherches Multidisciplinaires sur les Peptides (IFRMP 23), Institut National de la Santé et de la Recherche Médicale (INSERM)-CRLCC Henri Becquerel-Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU)-Université Le Havre Normandie (ULH), Normandie Université (NU)-CHU Rouen, Normandie Université (NU)-Centre National de la Recherche Scientifique (CNRS), Laboratoire de Logique, Algorithmique et Informatique (LLAIC1), Université d'Auvergne - Clermont-Ferrand I (UdA), Unité de Recherche en Génétique et Amélioration des Plantes (UR254), Institut National de la Recherche Agronomique (INRA), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU), CHU Rouen, Normandie Université (NU)-Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-CRLCC Henri Becquerel-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Normandie Université (NU)-Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre de Lutte Contre le Cancer Henri Becquerel Normandie Rouen (CLCC Henri Becquerel)-Université de Rouen Normandie (UNIROUEN), Neuroendocrinologie cellulaire et moléculaire, Télécom SudParis (TSP), Airbus Defence and Space [Toulouse], Université Laval [Québec] (ULaval), Leprince, Jérôme, Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-High-tech Research Infrastructures for Life Sciences (HeRacLeS), Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-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), and Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre de Lutte Contre le Cancer Henri Becquerel Normandie Rouen (CLCC Henri Becquerel)-Centre National de la Recherche Scientifique (CNRS)

Subjects
Male, MESH: Feedback, Physiological, [SDV.NEU.NB]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Neurobiology, Appetite Stimulants, [CHIM.THER]Chemical Sciences/Medicinal Chemistry, [SDV.BC.IC] Life Sciences [q-bio]/Cellular Biology/Cell Behavior [q-bio.CB], MESH: Neuropeptides, Synaptic Transmission, MESH: Appetitive Behavior, MESH: Arcuate Nucleus of Hypothalamus, Tissue Culture Techniques, MESH: Appetite Depressants, [SDV.BC.IC]Life Sciences [q-bio]/Cellular Biology/Cell Behavior [q-bio.CB], MESH: Animals, MESH: Nerve Tissue Proteins, MESH: Peptide Fragments, Diazepam Binding Inhibitor, Feedback, Physiological, Appetitive Behavior, MESH: Appetite Stimulants, Receptors, Melanocortin, MESH: Gene Expression Regulation, MESH: Glucose, [SDV.SP.PHARMA] Life Sciences [q-bio]/Pharmaceutical sciences/Pharmacology, MESH: Neuroglia, MESH: Injections, Intraventricular, Neuroglia, Signal Transduction, MESH: Rats, [CHIM.THER] Chemical Sciences/Medicinal Chemistry, Hypothalamus, Nerve Tissue Proteins, Appetite Depressants, MESH: Synaptic Transmission, Animals, [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology, MESH: Tissue Culture Techniques, Rats, Wistar, MESH: Receptors, Melanocortin, Injections, Intraventricular, Appetite Regulation, Neuropeptides, [SDV.NEU.NB] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Neurobiology, Arcuate Nucleus of Hypothalamus, MESH: Rats, Wistar, MESH: Hypothalamus, MESH: Male, Peptide Fragments, Rats, Glucose, Gene Expression Regulation, MESH: Protein Processing, Post-Translational, [SDV.SP.PHARMA]Life Sciences [q-bio]/Pharmaceutical sciences/Pharmacology, MESH: Diazepam Binding Inhibitor, Protein Processing, Post-Translational, MESH: Appetite Regulation
Abstract

International audience; Hypothalamic glucose sensing is involved in the control of feeding behavior and peripheral glucose homeostasis, and glial cells are suggested to play an important role in this process. Diazepam-binding inhibitor (DBI) and its processing product the octadecaneuropeptide (ODN), collectively named endozepines, are secreted by astroglia, and ODN is a potent anorexigenic factor. Therefore, we investigated the involvement of endozepines in brain glucose sensing. First, we showed that intracerebroventricular administration of glucose in rats increases DBI expression in hypothalamic glial-like tanycytes. We then demonstrated that glucose stimulates endozepine secretion from hypothalamic explants. Feeding experiments indicate that the anorexigenic effect of central administration of glucose was blunted by coinjection of an ODN antagonist. Conversely, the hyperphagic response elicited by central glucoprivation was suppressed by an ODN agonist. The anorexigenic effects of centrally injected glucose or ODN agonist were suppressed by blockade of the melanocortin-3/4 receptors, suggesting that glucose sensing involves endozepinergic control of the melanocortin pathway. Finally, we found that brain endozepines modulate blood glucose levels, suggesting their involvement in a feedback loop controlling whole-body glucose homeostasis. Collectively, these data indicate that endozepines are a critical relay in brain glucose sensing and potentially new targets in treatment of metabolic disorders.

Published
2013

6. HIV-1 clade promoters strongly influence spatial and temporal dynamics of viral replication in vivo

Author

Mireille Centlivre, Peter Sommer, Marie Michel, Raphaël Ho Tsong Fang, Sandrine Gofflo, Jenny Valladeau, Nathalie Schmitt, Françoise Thierry, Bruno Hurtrel, Simon Wain-Hobson, Monica Sala, Rétrovirologie Moléculaire, Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS), Biologie Cellulaire du Noyau (BCN), Physiopathologie des Infections Lentivirales, Hôpital Edouard Herriot [CHU - HCL], Hospices Civils de Lyon (HCL), Biologie des Rétrovirus, Institut Pasteur [Paris] (IP), Expression Génétique et Maladies, Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS), Institut Pasteur [Paris], and Medical Microbiology and Infection Prevention

Subjects
Simian Acquired Immunodeficiency Syndrome, MESH: NF-kappa B, HIV Infections, Virus Replication, Tissue Culture Techniques, MESH: HIV-1, MESH: Capsid, MESH: Animals, Promoter Regions, Genetic, MESH: Organ Specificity, MESH: Receptors, Cell Surface, 0303 health sciences, MESH: Infant, Newborn, NF-kappa B, General Medicine, MESH: HIV Infections, MESH: Transcription Factor AP-1, 3. Good health, MESH: Promoter Regions (Genetics), Organ Specificity, [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology, Simian Immunodeficiency Virus, MESH: Simian Acquired Immunodeficiency Syndrome, MESH: Simian immunodeficiency virus, Receptors, Cell Surface, Thymus Gland, Article, MESH: Macaca mulatta, 03 medical and health sciences, Capsid, Organ Culture Techniques, Species Specificity, MESH: Polymorphism, Genetic, Animals, Humans, MESH: Species Specificity, MESH: Tissue Culture Techniques, 030304 developmental biology, Polymorphism, Genetic, MESH: Humans, 030306 microbiology, Interleukin-7, MESH: Virus Replication, Infant, Newborn, MESH: Thymus Gland, Macaca mulatta, MESH: Interleukin-7, MESH: Organ Culture Techniques, Transcription Factor AP-1, HIV-1
Abstract

International audience; Although the primary determinant of cell tropism is the interaction of viral envelope or capsid proteins with cellular receptors, other viral elements can strongly modulate viral replication. While the HIV-1 promoter is polymorphic for a variety of transcription factor binding sites, the impact of these polymorphisms on viral replication in vivo is not known. To address this issue, we engineered isogenic SIVmac239 chimeras harboring the core promoter/enhancer from HIV-1 clades B, C, and E. Here it is shown that the clade C and E core promoters/enhancers bear a noncanonical activator protein-1 (AP-1) binding site, absent from the corresponding clade B region. Relative ex vivo replication of chimeras was strongly dependent on the tissue culture system used. Notably, in thymic histocultures, replication of the clade C chimera was favored by IL-7 enrichment, which suggests that the clade C polymorphism in the AP-1 and NF-kappaB binding sites is involved. Simultaneous infection of rhesus macaques with the 3 chimeras revealed a strong predominance of the clade C chimera during primary infection. Thereafter, the B chimera dominated in all tissues. These data show that the clade C promoter is particularly adapted to sustain viral replication in primary viremia and that clade-specific promoter polymorphisms constitute a major determinant for viral replication.

Published
2010

7. Genetic reactivation of cone photoreceptors restores visual responses in retinitis pigmentosa

Author

Erik Cabuy, Jens Duebel, Michel Paques, José-Alain Sahel, Valérie Forster, Martin Biel, Botond Roska, Peter Humphries, Didier Trono, Mathias Fradot, D. Balya, Serge Picaud, Karl Deisseroth, Sandra Siegert, Mathias W. Seeliger, Saddek Mohand-Said, Volker Busskamp, Anna C. Groner, Tim J. Viney, 'Frontiers in Genetics' program, Ecole Polytechnique Fédérale de Lausanne (EPFL)-National Center of Competence in Research, Neural Circuit Laboratories, Friedrich Miescher Institute for Biomedical Research, 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), School of Life Sciences, Ecole Polytechnique Fédérale de Lausanne (EPFL), Diagnostics Research Group, Eberhard-Karls University, Center for Integrated Protein Science (CIPSM), Technische Universität Munchen - Université Technique de Munich [Munich, Allemagne] (TUM)-Ludwig-Maximilians-Universität München (LMU)-Helmholtz Zentrum München = German Research Center for Environmental Health, Smurfit Institute of Genetics, Trinity College Dublin, Fondation Ophtalmologique Adolphe de Rothschild [Paris], Department of Bioengineering, Department of Psychiatry and Behavioral Sciences, Stanford University, Friedrich Miescher Institute, US Office of Naval Research Naval International Cooperative Opportunities in Science and Technology Program grant, Foundation Fighting Blindness (USA), Swiss National Science Foundation, National Centers of Competence in Research Frontiers in Genetics, ANR-07-TECS-0014,MEDINAS,Matrices d'Electrodes en Diamant pour l'Interfaçage Neuronal Appliqué à la Suppléance fonctionnelle (MEDINAS)(2007), European Project, Fondation Ophtalmologique Adolphe de Rothschild, Marazova, Katia, Technologies pour la santé - Matrices d'Electrodes en Diamant pour l'Interfaçage Neuronal Appliqué à la Suppléance fonctionnelle (MEDINAS) - - MEDINAS2007 - ANR-07-TECS-0014 - TECSAN - VALID, Marie Curie Excellence Grant, EU HEALTH-F2- 223156, RETICIRC - INCOMING, Technische Universität Munchen - Université Technique de Munich [Munich, Allemagne] (TUM)-Ludwig Maximilian University of Munich [Germany] (LMU München)-Helmholtz-Zentrum München (HZM), 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), and Technische Universität Munchen - Université Technique de Munich [Munich, Allemagne] (TUM)-Helmholtz-Zentrum München (HZM)-Ludwig Maximilian University of Munich [Germany] (LMU München)

Subjects
Retinal degeneration, Retinal Ganglion Cells, MESH: Evoked Potentials, Visual, genetic structures, Light, Serotypes, Expression, [SDV.GEN] Life Sciences [q-bio]/Genetics, MESH: Dependovirus, MESH: Mice, Knockout, Tissue Culture Techniques, chemistry.chemical_compound, Mice, 0302 clinical medicine, MESH: Genetic Vectors, MESH: Animals, Selectivity, Promoter Regions, Genetic, Halorhodopsin, Mice, Knockout, 0303 health sciences, Multidisciplinary, Halobacteriaceae, Visually guided, MESH: Retina, Retinal Degeneration, Anatomy, Dependovirus, 3. Good health, medicine.anatomical_structure, Retinal Cone Photoreceptor Cells, Halorhodopsins, Retinitis Pigmentosa, Visual phototransduction, MESH: Halorhodopsins, Movement, Genetic Vectors, Biology, Transfection, Retina, 03 medical and health sciences, MESH: Halobacteriaceae, Retinitis pigmentosa, MESH: Promoter Regions, Genetic, medicine, Animals, Humans, Visual Pathways, MESH: Tissue Culture Techniques, MESH: Vision, Ocular, MESH: Mice, Vision, Ocular, 030304 developmental biology, MESH: Visual Pathways, [SDV.GEN]Life Sciences [q-bio]/Genetics, MESH: Humans, Blindness, MESH: Transfection, Ganglion-Cells, Retinal, MESH: Retinal Ganglion Cells, Genetic Therapy, medicine.disease, MESH: Light, eye diseases, Disease Models, Animal, MESH: Retinal Cone Photoreceptor Cells, chemistry, Direction, MESH: Retinitis Pigmentosa, Evoked Potentials, Visual, sense organs, MESH: Disease Models, Animal, MESH: Gene Therapy, Neuroscience, 030217 neurology & neurosurgery, Model
Abstract

Let There Be Light Retinitis pigmentosa, a disease that can result from a wide variety of genetic defects, causes degeneration of photoreceptor cells in the retina and leads to blindness. In the course of the disease, it is generally the rod photoreceptor cells that degenerate first. Cone photoreceptor cells may persist, but in a damaged and nonfunctional state. Busskamp et al. (p. 413 , published online 24 June; see the cover; see the Perspective by Cepko ) have now applied a gene therapy approach to mouse models of retinitis pigmentosa. Inducing expression of a bacterial light-activated ion pump, halorho dopsin, in the damaged cone cells improved visual responses in the diseased mouse retinas. Thus, it may be possible to rescue cone photoreceptors therapeutically, even after they have already been damaged.

Published
2010

8. STOP proteins contribute to the maturation of the olfactory system

Author

Annie Schweitzer, Marion Richard, François Jourdan, Véronique Pellier-Monnin, Joëlle Sacquet, Annie Andrieux, Marion Jany, Neurosciences Sensorielles Comportement Cognition, Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS), IFR des neurosciences de Lyon (IFNL), Université de Lyon-Université de Lyon-Hospices Civils de Lyon (HCL)-Centre Hospitalier le Vinatier [Bron]-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Grenoble Institut des Neurosciences (GIN), Université Joseph Fourier - Grenoble 1 (UJF)-Institut National de la Santé et de la Recherche Médicale (INSERM), and Andrieux, Annie

Subjects
Olfactory system, MESH: Protein Isoforms, Microtubules, MESH: Mice, Knockout, MESH: Vomeronasal Organ, Tissue Culture Techniques, Mice, 0302 clinical medicine, Olfactory bulb, MESH: Pregnancy, Olfactory nerve, Pregnancy, Protein Isoforms, MESH: Animals, MESH: Nerve Tissue Proteins, Cytoskeleton, Mice, Knockout, Mice, Inbred BALB C, 0303 health sciences, Olfactory Pathways, Cell biology, medicine.anatomical_structure, Female, [SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], Vomeronasal Organ, Microtubule-Associated Proteins, MESH: Rats, MESH: Mice, Inbred BALB C, Nerve Tissue Proteins, Sensory system, Biology, Olfactory Receptor Neurons, 03 medical and health sciences, Cellular and Molecular Neuroscience, Microtubule, Neuropil, medicine, Animals, Axon outgrowth, [SDV.NEU] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], MESH: Tissue Culture Techniques, Rats, Wistar, Molecular Biology, MESH: Mice, 030304 developmental biology, Cell Biology, MESH: Rats, Wistar, MESH: Olfactory Receptor Neurons, Rats, MESH: Microtubule-Associated Proteins, nervous system, Olfactory ensheathing glia, Neuroscience, MESH: Female, 030217 neurology & neurosurgery, MESH: Olfactory Pathways
Abstract

International audience; Regulation of microtubule dynamics is crucial for axon growth and guidance as well as for the establishment of synaptic connections. STOPs (Stable Tubule Only Polypeptides) are microtubule-associated proteins that regulate microtubule stabilization but are also able to interact with actin or Golgi membranes. Here, we have investigated the involvement of STOPs during the development of the olfactory system. We first describe the spatio-temporal expression patterns of N- and E-STOP, the two neuronal-specific isoforms of STOP. E- and N-STOP are expressed in the axonal compartment of olfactory sensory neurons, but are differentially regulated during development. Interestingly, each neuronal isoform displays a specific gradient distribution within the olfactory nerve layer. Then, we have examined the development of the olfactory system in the absence of STOPs. Olfactory axons display a normal outgrowth and targeting in STOP-null mice, but maturation of the synapses in the glomerular neuropil is altered.

Published
2009

9. Secretion of adiponectin multimeric complexes from adipose tissue explants is not modified by very low calorie diet

Author

Lenka Rossmeislová, Zuzana Hnevkovska, Magda Bajzova, Zuzana Kovacova, Jan Polak, Michaela Vitkova, Dominique Langin, Vladimir Stich, Michaela Kovacikova, Eva Klimcakova, Sports Medicine Department, Third Faculty of Medicine Charles University, Division of Cell and Molecular Biology, Franco-Czech Laboratory for Clinical Research on Obesity, Charles University [Prague] (CU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Internal Medicine Department, Vinohrady Teatching Hospital, Institut de médecine moléculaire de Rangueil (I2MR), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-IFR150-Institut National de la Santé et de la Recherche Médicale (INSERM), Laboratoire de Biochimie [Purpan], Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-CHU Toulouse [Toulouse]-Institut Fédératif de Biologie (IFB) - Hôpital Purpan, Hôpital Purpan [Toulouse], CHU Toulouse [Toulouse]-CHU Toulouse [Toulouse]-Hôpital Purpan [Toulouse], CHU Toulouse [Toulouse], Simon, Marie Francoise, Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées- Institut Fédératif de Recherche Bio-médicale Institution (IFR150)-Institut National de la Santé et de la Recherche Médicale (INSERM), Laboratoire de Biochimie [CHU Toulouse], Institut Fédératif de Biologie (IFB), Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Pôle Biologie [CHU Toulouse], and Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)

Subjects
Male, Luminescence, Polymers, Endocrinology, Diabetes and Metabolism, Adipose tissue, Tissue Culture Techniques, 0302 clinical medicine, Endocrinology, Weight loss, Blood plasma, MESH: Obesity, 2. Zero hunger, 0303 health sciences, medicine.diagnostic_test, MESH: Kinetics, MESH: Luminescence, MESH: Molecular Weight, MESH: Waist-Hip Ratio, Biopsy, Needle, MESH: Enzyme-Linked Immunosorbent Assay, General Medicine, MESH: Adiponectin, 3. Good health, MESH: Polymers, Very low calorie diet, Adipose Tissue, Female, Adiponectin, medicine.symptom, MESH: Adipose Tissue, Adult, medicine.medical_specialty, MESH: Biopsy, Needle, food.diet, Blotting, Western, 030209 endocrinology & metabolism, Enzyme-Linked Immunosorbent Assay, Biology, 03 medical and health sciences, MESH: Weight Loss, food, Western blot, Internal medicine, MESH: Body Height, Weight Loss, medicine, Humans, MESH: Blotting, Western, Secretion, Obesity, MESH: Tissue Culture Techniques, 030304 developmental biology, Caloric Restriction, MESH: Caloric Restriction, MESH: Humans, Waist-Hip Ratio, Body Weight, MESH: Adult, medicine.disease, Body Height, MESH: Male, Culture Media, MESH: Body Weight, Molecular Weight, Kinetics, MESH: Culture Media, MESH: Female
Abstract

ObjectiveAdiponectin is a protein abundantly secreted by the adipose tissue (AT). Plasma adiponectin levels are decreased in obese, insulin-resistant, and type 2 diabetic patients. Various multimeric complexes, i.e. high-, middle-, and low-molecular weight isoforms (HMW, MMW and LMW), are present in plasma. Here, we investigated the effect of weight reducing diet on the distribution of adiponectin isoforms in plasma and on their secretion in AT explants from obese subjects.DesignA total of 20 obese subjects (age 37.8±7.3 years, body mass index 33.9±5.0 kg/m2) underwent eight weeks of very low-calorie diet (VLCD). A needle biopsy of subcutaneous abdominal AT and blood samples were taken before and after dietary intervention. AT explants were incubated in culture medium for 4 h. ELISA assay and western blot analyses were used to identify adiponectin complexes in culture media and in plasma.ResultsThe distribution of adiponectin polymers in plasma was different from that secreted in human AT explants. Before VLCD, the relative amount of HMW isoform was 75.5±9.1% of total adiponectin in culture media and 52.2±11.2% in plasma. Despite the diet-induced weight loss and improvement of insulin sensitivity, VLCD neither induced change in total adiponectin level nor in the ratio of HMW to total adiponectin in plasma and in culture media of AT explants.ConclusionsThe profile of adiponectin polymeric isoforms secreted by AT explants into culture media differs from the plasma profile. A dietary intervention leading to weight loss and improvement of insulin sensitivity was not associated with modifications of AT secretion of total or HMW adiponectin.

Published
2009

10. First evidence of aerobic biodegradation of BTEX compounds by pure cultures of Marinobacter

Author

Jean-Luc Tholozan, Richard Auria, Jean Luc Cayol, Sophie Laveau, Frédéric Verhé, Bernard Ollivier, Sabrina Berlendis, Laboratoire de Microbiologie et Biotechnologie des Environnements Chauds, and Université de la Méditerranée - Aix-Marseille 2-Université de Provence - Aix-Marseille 1

Subjects
Toluene biodegradation, hydrocarbonoclasticus, BTEX, Sodium Chloride, medicine.disease_cause, MESH: Benzene Derivatives: metabolism, Applied Microbiology and Biotechnology, Biochemistry, Ethylbenzene, Tissue Culture Techniques, chemistry.chemical_compound, MESH: Biomass, MESH: Toluene: metabolism, Benzene Derivatives, Biomass, Marinobacter hydrocarbonoclasticus, Benzene, MESH: Carbon Dioxide: metabolism, 0303 health sciences, Marinobacter vinifirmus, biology, MESH: Sodium Chloride: chemistry, General Medicine, 6. Clean water, Bacteria, Aerobic, Energy source, MESH: Benzene: metabolism, Biotechnology, Bioengineering, Xylenes, MESH: Bacteria, Aerobic: chemistry,metabolism, Microbiology, 03 medical and health sciences, [SDV.EE.ECO]Life Sciences [q-bio]/Ecology, environment/Ecosystems, Marinobacter, medicine, MESH: Tissue Culture Techniques, Molecular Biology, 030304 developmental biology, MESH: Xylenes: metabolism, 030306 microbiology, Aerobic, Halophilic bacterium, Carbon Dioxide, biology.organism_classification, Toluene, MESH: Marinobacter: chemistry,metabolism, chemistry, 13. Climate action, Nuclear chemistry
Abstract

Marinobacter vinifirmus was shown to degrade toluene as sole carbon and energy source under aerobiosis and at NaCl concentrations in the range 30-150 g/L. Maximum toluene consumption rate, total CO2, and biomass productions were measured in the presence of 60 g/L of NaCl. Under these conditions, 90% of the carbon from toluene was recovered as CO2 and biomass. Maximum specific toluene consumption rate was about 0.12 mgC toluene mgC biomass(-1) h(-1) at NaCl concentrations between 30 and 60 g/L. It decreased to 0.03 mgC toluene mgC biomass(-1) h(-1) at 150 g/L. Besides toluene, M. vinifirmus degraded benzene, ethylbenzene, and p-xylene. Benzene and toluene were utilized to a lesser extent by another Marinobacter sp., Marinobacter hydrocarbonoclasticus.

Published
2009

11. Toward Safer Thrombolytic Agents in Stroke: Molecular Requirements for NMDA Receptor-Mediated Neurotoxicity

Author

Ronan Bureau, Denis Vivien, José P. López-Atalaya, Jana Sopkova-de Oliveira Santos, Benoit D. Roussel, Hervé Castel, Karl-Uwe Petersen, Jérôme Parcq, Carine Ali, Karim Benchenane, Denis Levrat, Sylvain Rault, Hubert Vaudry, Olivier Nicole, Jérôme Leprince, Yannick Hommet, Denis To Van, Sérine protéases et physiopathologie de l'unité neurovasculaire, Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre-Imagerie, Neurosciences, et Application aux Pathologies (CI-NAPS - UMR 6232), Normandie Université (NU)-Normandie Université (NU)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-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 d'Etudes et de Recherche sur le Médicament de Normandie (CERMN), Normandie Université (NU)-Normandie Université (NU), Neuroendocrinologie cellulaire et moléculaire, Université de Rouen Normandie (UNIROUEN), Institut Fédératif de Recherches Multidisciplinaires sur les Peptides (IFRMP 23), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre de Lutte Contre le Cancer Henri Becquerel Normandie Rouen (CLCC Henri Becquerel)-Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU)-Université Le Havre Normandie (ULH), Normandie Université (NU)-CHU Rouen, Normandie Université (NU)-Centre National de la Recherche Scientifique (CNRS), Biacore AB, PAION Deutschland GmbH, Institut National de la Santé et de la Recherche Médicale (INSERM)-CRLCC Henri Becquerel-Université de Rouen Normandie (UNIROUEN), CHU Rouen, Normandie Université (NU)-Université de Rouen Normandie (UNIROUEN), and Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre de Lutte Contre le Cancer Henri Becquerel Normandie Rouen (CLCC Henri Becquerel)-Centre National de la Recherche Scientifique (CNRS)

Subjects
Models, Molecular, MESH: Signal Transduction, MESH: Protein Structure, Quaternary, [SDV.NEU.NB]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Neurobiology, Excitotoxicity, MESH: Neurons, MESH: Catalytic Domain, Reteplase, MESH: Amino Acid Sequence, [CHIM.THER]Chemical Sciences/Medicinal Chemistry, Pharmacology, medicine.disease_cause, Tissue plasminogen activator, Tissue Culture Techniques, Mice, 0302 clinical medicine, Catalytic Domain, MESH: Tissue Plasminogen Activator, [SDV.BC.IC]Life Sciences [q-bio]/Cellular Biology/Cell Behavior [q-bio.CB], Desmoteplase, MESH: Fibrinolytic Agents, MESH: Animals, Cells, Cultured, Neurons, 0303 health sciences, MESH: Plasminogen Activators, MESH: Drug-Related Side Effects and Adverse Reactions, 3. Good health, Stroke, Neurology, Tissue Plasminogen Activator, NMDA receptor, Cardiology and Cardiovascular Medicine, MESH: Models, Molecular, medicine.drug, Protein Binding, Signal Transduction, MESH: Cells, Cultured, Drug-Related Side Effects and Adverse Reactions, Molecular Sequence Data, Receptors, N-Methyl-D-Aspartate, MESH: Stroke, 03 medical and health sciences, Plasminogen Activators, Fibrinolytic Agents, medicine, Animals, MESH: Protein Binding, Amino Acid Sequence, MESH: Tissue Culture Techniques, Protein Structure, Quaternary, MESH: Mice, 030304 developmental biology, MESH: Receptors, N-Methyl-D-Aspartate, MESH: Molecular Sequence Data, business.industry, Neurotoxicity, medicine.disease, [SDV.SP.PHARMA]Life Sciences [q-bio]/Pharmaceutical sciences/Pharmacology, Neurology (clinical), business, Neuroscience, Plasminogen activator, 030217 neurology & neurosurgery, Fibrinolytic agent
Abstract

Current thrombolytic therapy for acute ischemic stroke with tissue-type plasminogen activator (tPA) has clear global benefits. Nevertheless, evidences argue that in addition to its prohemorrhagic effect, tPA might enhance excitotoxic necrosis. In the brain parenchyma, tPA, by binding to and then cleaving the amino-terminal domain (ATD) of the NR1 subunit of N-methyl-D-aspartate (NMDA) glutamate receptors, increases calcium influx to toxic levels. We show here that tPA binds the ATD of the NR1 subunit by a two-sites system (KD=24 nmol/L). Although tenecteplase (TNK) and reteplase also display two-sites binding profiles, the catalytically inactive mutant TNKS478A displays a one-site binding profile and desmoteplase (DSPA), a kringle 2 (K2) domain-free plasminogen activator derived from vampire bat, does not interact with NR1. Moreover, we show that in contrast to tPA, DSPA does not promote excitotoxicity. These findings, together with three-dimensional (3D) modeling, show that a critical step for interaction of tPA with NR1 is the binding of its K2 domain, followed by the binding of its catalytic domain, which in turn cleaves the NR1 subunit at its ATD, leading to a subsequent potentiation of NMDA-induced calcium influx and neurotoxicity. This could help design safer new generation thrombolytic agents for stroke treatment. © 2008 ISCBFM All rights reserved., This work was supported by grants from INSERM, the French Ministry of Research and Technology, the Regional Council of Lower Normandy, the Regional Platform for Cell Imaging of Upper Normandy, the Medical Research Foundation, the University of Caen, Fonds Europeéns de Développement Régional, the Paul Hamel Foundation, the Diagnosis in Molecular Imaging Program (FP6-project DiMI-LSHB-CT-2005-512146-), and PAION Deutschland GmbH.

Published
2008

12. Ex Vivo bone formation in bovine trabecular bone cultured in a dynamic 3D bioreactor is enhanced by compressive mechanical strain

Author

Alain Guignandon, V. Mann, Aline Martin, Brendon Noble, Luc Malaval, Valentin David, Laurence Vico, Marie-Hélène Lafage-Proust, Aline Rattner, David Jones, Vico, Laurence, Contraintes mécaniques et tissu osseux, Université Jean Monnet [Saint-Étienne] (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM), Tissu Osseux et Contraintes Mecaniques (LBTO), Scottish Mechanotransduction Consortium, University of Edinburgh, Experimental Orthopaedics and Biomechanics, and Philipps University

Subjects
Time Factors, Compressive Strength, medicine.medical_treatment, Osteoclasts, 02 engineering and technology, Biochemistry, Bone remodeling, Tissue Culture Techniques, MESH: Bioreactors, Bioreactors, Osteogenesis, MESH: Osteoclasts, MESH: Animals, MESH: Osteogenesis, 0303 health sciences, [SDV.MHEP.RSOA] Life Sciences [q-bio]/Human health and pathology/Rhumatology and musculoskeletal system, MESH: Stress, Mechanical, Chemistry, Osteoblast, Cell Differentiation, MESH: Bone and Bones, MESH: Cattle, medicine.anatomical_structure, [SDV.MHEP.RSOA]Life Sciences [q-bio]/Human health and pathology/Rhumatology and musculoskeletal system, Osteocyte, Bone Remodeling, Cancellous bone, MESH: Cell Differentiation, 0206 medical engineering, Biomedical Engineering, Bioengineering, Bone and Bones, Biomaterials, 03 medical and health sciences, In vivo, Osteoclast, MESH: Bone Remodeling, medicine, Animals, MESH: Tissue Culture Techniques, 030304 developmental biology, MESH: Osteoblasts, Osteoblasts, MESH: Time Factors, MESH: Compressive Strength, Bisphosphonate, 020601 biomedical engineering, Cattle, Stress, Mechanical, Ex vivo, Biomedical engineering
Abstract

Our aim was to test cell and trabecular responses to mechanical loading in vitro in a tissue bone explant culture model. We used a new three-dimensional culture model, the ZetOS system, which provides the ability to exert cyclic compression on cancellous bone cylinders (bovine sternum) cultured in forced flow circumfusion chambers, and allows to assess mechanical parameters of the cultivated samples. We evaluated bone cellular parameters through osteocyte viability test, gene and protein expression, and histomorphometric bone formation rate, in nonloaded versus loaded samples. The microarchitecture of bone cores was appraised by in vivo micro-CT imaging. After 3 weeks, the samples receiving daily cyclic compression exhibited increased osteoblast differentiation and activity associated with thicker, more plate-like-shaped trabeculae and higher Young's modulus and ultimate force as compared to unloaded samples. Osteoclast activity was not affected by mechanical strain, although it was responsive to drug treatments (retinoic acid and bisphosphonate) during the first 2 weeks of culture. Thus, in the ZetOS apparatus, we reproduce in vitro the osteogenic effects of mechanical strain known in vivo, making this system a unique and an essential laboratory aid for ex vivo testing of lamellar bone remodeling.

Published
2008

13. Coxsackie adenovirus receptor and alpha nu beta3/alpha nu beta5 integrins in adenovirus gene transfer of rat cochlea

Author

Venail, Frédéric, Wang, Jing, Ruel, Jérôme, Ballana, Ester, Rebillard, Guy, Eybalin, Michel, Arbones, M., Bosch, A., Puel, Jean-Luc, Physiopathologie et thérapie des déficits sensoriels et moteurs, Université Montpellier 2 - Sciences et Techniques (UM2)-IFR76-Institut National de la Santé et de la Recherche Médicale (INSERM), Laboratoire d'Anatomie [CHU Montpellier], Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Genes and Disease Program, Centre de Regulacio´ Geno´mica-CRG-UPF, Department of Biochemistry and Molecular Biology, Centre of Animal Biotechnology and Gene Therapy (CBATEG), Universitat Autònoma de Barcelona (UAB), and Hamel, Christian

Subjects
MESH: Integrin beta3, Integrins, Integrin beta Chains, Action Potentials, Gene Expression, MESH: Microscopy, Fluorescence, Integrin alpha5, Tissue Culture Techniques, Transduction, Genetic, MESH: Genetic Vectors, MESH: Cochlea, MESH: Integrin beta Chains, MESH: Animals, Transgenes, MESH: Action Potentials, Integrin beta3, MESH: Adenoviridae, MESH: Integrins, MESH: Transduction, Genetic, Immunohistochemistry, Cochlea, MESH: Models, Animal, Models, Animal, Receptors, Virus, [SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], MESH: Integrin alpha5, Coxsackie and Adenovirus Receptor-Like Membrane Protein, MESH: Gene Expression, MESH: Rats, Genetic Vectors, Green Fluorescent Proteins, MESH: Transgenes, Adenoviridae, Injections, MESH: Green Fluorescent Proteins, otorhinolaryngologic diseases, Animals, Humans, MESH: Injections, [SDV.NEU] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], MESH: Tissue Culture Techniques, Rats, Wistar, Cochlear Nerve, MESH: Cochlear Nerve, MESH: Humans, MESH: Immunohistochemistry, Genetic Therapy, MESH: Rats, Wistar, MESH: Receptors, Virus, Rats, Microscopy, Fluorescence, MESH: Gene Therapy
Abstract

International audience; This study was designed to determine whether Coxsackie adenovirus receptor (CAR) and alpha nu beta3/alpha nu beta5 integrin co-receptors are involved in adenovirus gene transfer in the rat cochlea. We find that CAR and integrin co-receptors are expressed in every cell subtype transduced by the adenoviral vector Ad5 DeltaE1-E3/cytomegalovirus/green fluorescent protein (GFP) on cochlear slices in vitro. The spiral ganglion neurons, which do not express CAR, were not transduced by the virus. Blocking these receptors by monoclonal antibodies decreased transgene expression, whereas disrupting tight junctions with ethylenediaminetetraacetic acid led to an increased transgene expression. However, sensory hair cells and strial cells also expressing CAR and alpha nu integrins were not transduced by the vector. GFP expression was also studied in vivo. Perilymphatic perfusion of adenovirus in vivo did not affect hearing and only cells lining the perilymphatic spaces were transduced. Endolymphatic perfusion resulted in low-frequency hearing loss and although some cells of the organ of Corti were efficiently transduced, the sensory and the strial cells were not. Transduced sensory and strial cells were occasionally observed in cochleas after single shot of adenovirus. Pretreatment with anti-CAR and anti-alpha nu antibodies decreases GFP expression in vivo, suggesting that the CAR/alpha nu integrin pathway is involved in adenovirus transduction in the cochlea.

Published
2007

14. Loss of AP-3 function affects spontaneous and evoked release at hippocampal mossy fiber synapses

Author

Rachel Rudge, Anita Scheuber, Thierry Galli, Graça Raposo, Jean Christophe Poncer, Thomas Binz, Lydia Danglot, Cortex et Epilepsie [Paris], CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC), Institut Jacques Monod (IJM (UMR_7592)), Université Paris Diderot - Paris 7 (UPD7)-Centre National de la Recherche Scientifique (CNRS), Compartimentation et dynamique cellulaires (CDC), Centre National de la Recherche Scientifique (CNRS)-Institut Curie [Paris]-Université Pierre et Marie Curie - Paris 6 (UPMC), Institut für Biochemie, Medizinische Hochschule Hannover (MHH), INSERM (Avenir Program) - European Commission (‘Signaling and Traffic' STREP 503229) - Association Française contre les Myopathies - Ministère de la Recherche (ACI-BDP) - -Fondation pour la Recherche Médicale – HFSP (RGY0027/2001-B101) - Fondation pour la Recherche sur le Cerveau, Kropfinger, Antonia, Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), and Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut Curie [Paris]-Centre National de la Recherche Scientifique (CNRS)

Subjects
Quantitative Biology - Subcellular Processes, [SDV.BC.BC]Life Sciences [q-bio]/Cellular Biology/Subcellular Processes [q-bio.SC], Hippocampal formation, Synaptic Transmission, Calcium in biology, MESH: Synapses, Tissue Culture Techniques, Mice, chemistry.chemical_compound, 0302 clinical medicine, MESH: Animals, Neurotransmitter, Hippocampal mossy fiber, 0303 health sciences, Multidisciplinary, MESH: Electrophysiology, Chemistry, MESH: Transcription Factors, Biological Sciences, Cell biology, DNA-Binding Proteins, Electrophysiology, MESH: Calcium, Mossy Fibers, Hippocampal, Neurons and Cognition (q-bio.NC), [SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], Adaptor Protein Complex 3, Endosome, MESH: Mice, Transgenic, Mice, Transgenic, Neurotransmission, Sensitivity and Specificity, Synaptic vesicle, Exocytosis, 03 medical and health sciences, Osmotic Pressure, [SDV.BC.BC] Life Sciences [q-bio]/Cellular Biology/Subcellular Processes [q-bio.SC], MESH: Synaptic Transmission, Animals, [SDV.NEU] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], MESH: Tissue Culture Techniques, Subcellular Processes (q-bio.SC), MESH: Mice, 030304 developmental biology, Brefeldin A, MESH: Brefeldin A, MESH: Mossy Fibers, Hippocampal, MESH: Osmotic Pressure, MESH: Sensitivity and Specificity, FOS: Biological sciences, Quantitative Biology - Neurons and Cognition, Synapses, Calcium, Neuroscience, 030217 neurology & neurosurgery, MESH: DNA-Binding Proteins, Transcription Factors
Abstract

Synaptic vesicle (SV) exocytosis mediating neurotransmitter release occurs spontaneously at low intraterminal calcium concentrations and is stimulated by a rise in intracellular calcium. Exocytosis is compensated for by the reformation of vesicles at plasma membrane and endosomes. Although the adaptor complex AP-3 was proposed to be involved in the formation of SVs from endosomes, whether its function has an indirect effect on exocytosis remains unknown. Using mocha mice, which are deficient in functional AP-3, we identify an AP-3-dependent tetanus neurotoxin-resistant asynchronous release that can be evoked at hippocampal mossy fiber (MF) synapses. Presynaptic targeting of the tetanus neurotoxin-resistant vesicle soluble N -ethylmaleimide-sensitive factor attachment protein receptor (SNARE) tetanus neurotoxin-insensitive vesicle-associated membrane protein (TI-VAMP) is lost in mocha hippocampal MF terminals, whereas the localization of synaptobrevin 2 is unaffected. In addition, quantal release in mocha cultures is more frequent and more sensitive to sucrose. We conclude that lack of AP-3 results in more constitutive secretion and loss of an asynchronous evoked release component, suggesting an important function of AP-3 in regulating SV exocytosis at MF terminals.

Published
2006

15. Host cell responses induced by hepatitis C virus binding.: Host cell responses induced by HCV

Author

Fang, Xinhua, Zeisel, Mirjam B, Wilpert, Jochen, Gissler, Bettina, Thimme, Robert, Kreutz, Clemens, Maiwald, Thomas, Timmer, Jens, Kern, Winfried, Donauer, Johannes, Geyer, Marcel, Walz, Gerd, Depla, Erik, von Weizsäcker, Fritz, Blum, Hubert, Baumert, Thomas, Department of Medicine II, University of Freiburg [Freiburg], Center for Data Analysis and Modeling and Dept. of Physics, Department of Medicine IV, Innogenetics N.V., Innogenetics group, Interaction virus-hôte et maladies du foie, Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM), QLK-2-CT-1999-00356, QLK-2-CT-2002-01329 and VIRGIL Network of Excellence, Deutsche Forschungsgemeinschaft (Ba1417/11-1), and Baumert, Thomas F.

Subjects
MESH: Hepatitis C, MESH: Molecular Sequence Data, MESH: Cell Line, Tumor, MESH: Humans, virus-host interaction, MESH: Protein Array Analysis, receptor, MESH: Carrier Proteins, [SDV.MHEP.HEG]Life Sciences [q-bio]/Human health and pathology/Hépatology and Gastroenterology, MESH: Base Sequence, MESH: Host Cell Factor C1, MESH: Gene Expression Regulation, digestive system diseases, infection, MESH: Sensitivity and Specificity, [SDV.MHEP.HEG] Life Sciences [q-bio]/Human health and pathology/Hépatology and Gastroenterology, MESH: RNA, Viral, MESH: Reverse Transcriptase Polymerase Chain Reaction, MESH: Viral Envelope Proteins, hepatitis, MESH: Hepacivirus, MESH: Tissue Culture Techniques, signalling, MESH: Antigens, Viral, MESH: Cells, Cultured
Abstract

International audience; Initiation of hepatitis C virus (HCV) infection is mediated by docking of the viral envelope to the hepatocyte cell surface membrane followed by entry of the virus into the host cell. Aiming to elucidate the impact of this interaction on host cell biology, we performed a genomic analysis of the host cell response following binding of HCV to cell surface proteins. As ligands for HCV-host cell surface interaction, we used recombinant envelope glycoproteins and HCV-like particles (HCV-LPs) recently shown to bind or enter hepatocytes and human hepatoma cells. Gene expression profiling of HepG2 hepatoma cells following binding of E1/E2, HCV-LPs, and liver tissue samples from HCV-infected individuals was performed using a 7.5-kd human cDNA microarray. Cellular binding of HCV-LPs to hepatoma cells resulted in differential expression of 565 out of 7,419 host cell genes. Examination of transcriptional changes revealed a broad and complex transcriptional program induced by ligand binding to target cells. Expression of several genes important for innate immune responses and lipid metabolism was significantly modulated by ligand-cell surface interaction. To assess the functional relevance and biological significance of these findings for viral infection in vivo, transcriptional changes were compared with gene expression profiles in liver tissue samples from HCV-infected patients or controls. Side-by-side analysis revealed that the expression of 27 genes was similarly altered following HCV-LP binding in hepatoma cells and viral infection in vivo. In conclusion, HCV binding results in a cascade of intracellular signals modulating target gene expression and contributing to host cell responses in vivo. Reprogramming of cellular gene expression induced by HCV-cell surface interaction may be part of the viral strategy to condition viral entry and replication and escape from innate host cell responses.

Published
2006

16. Creatine supplementation improves dopaminergic cell survival and protects against MPP+ toxicity in an organotypic tissue culture system

Author

Sandra H. Krebs, Hans Rudolf Widmer, Rolf W. Seiler, Angélique Ducray, Alberto Pérez-Bouza, Uwe Schlattner, Alexander W. Huber, Theo Wallimann, Robert H. Andres, Department of Neurosurgery, Université de Berne, Laboratoire de bioénergétique fondamentale et appliquée (LBFA), Université Joseph Fourier - Grenoble 1 (UJF)-Institut National de la Santé et de la Recherche Médicale (INSERM), Department of Biology, Eidgenössische Technische Hochschule - Swiss Federal Institute of Technology [Zürich] (ETH Zürich)-Institute of Cell Biology, Hamant, Sarah, Universität Bern [Bern] (UNIBE), and Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Joseph Fourier - Grenoble 1 (UJF)

Subjects
0301 basic medicine, 1-Methyl-4-phenylpyridinium, lcsh:Medicine, MESH: Rats, Sprague-Dawley, Rats, Sprague-Dawley, Tissue Culture Techniques, chemistry.chemical_compound, 0302 clinical medicine, MESH: Pregnancy, Mesencephalon, Pregnancy, MESH: Animals, Cells, Cultured, MESH: 1-Methyl-4-phenylpyridinium, MESH: Creatine, Kinase, MESH: Cell Survival, Female, MESH: Cells, Cultured, Programmed cell death, medicine.medical_specialty, MESH: Rats, Cell Survival, Biomedical Engineering, Biology, Creatine, Neuroprotection, 03 medical and health sciences, Internal medicine, Precursor cell, Dopaminergic Cell, medicine, [SDV.BBM] Life Sciences [q-bio]/Biochemistry, Molecular Biology, Animals, Humans, [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology, MESH: Tissue Culture Techniques, Transplantation, MESH: Humans, Tyrosine hydroxylase, lcsh:R, Cell Biology, MESH: Mesencephalon, Rats, 030104 developmental biology, Endocrinology, chemistry, MESH: Female, 030217 neurology & neurosurgery
Abstract

International audience; Cell replacement therapy using mesencephalic precursor cells is an experimental approach for the treatment of Parkinson's disease (PD). A significant problem associated with this procedure is the poor survival of grafted neurons. Impaired energy metabolism is considered to contribute to neuronal cell death after transplantation. Creatine is a substrate for mitochondrial and cytosolic creatine kinases (CK) and buffers cellular ATP resources. Furthermore, elevated cellular creatine levels facilitate metabolic channeling and show antiapoptotic properties. Exogenous creatine supplementation therefore might offer a tool for improvement of dopaminergic neuron survival. The present study aimed at investigating the effects of creatine on cell survival of rat embryonic day 14 (E14) ventral mesencephalic neurons grown as organotypic free-floating roller tube (FFRT) cultures. We found that the brain-specific isoform of CK (BB-CK) and the ubiquitous mitochondrial isoform (uMt-CK) are expressed at high levels in FFRT cultures and colocalize with tyrosine hydroxylase immunoreactive (TH-ir) cells. Exposure of these cultures to creatine induced an increase in the content of the BB-CK isotype. Creatine (5 mM) administration starting at day in vitro (DIV) 7 resulted in a significant increase (+35%) in TH-ir cell density at DIV21. In addition, we observed that creatine treatment provided neuroprotection against 1-methyl-4-phenyl pyridinium ion (MPP+)-induced TH-ir cell loss in the FFRT culture system, resulting in a significantly higher density (+19%) of TH-ir neurons in creatine-treated cultures compared to corresponding controls. The decrease of TH-ir neurons in the MPP+-treated group corresponded with an increase in immunoreactivity for active caspase-3, an effect that was not seen in the group receiving creatine supplementation. In conclusion, our data imply that creatine administration is beneficial for the survival of TH-ir neurons encountering harmful conditions.

Published
2005

17. Evidence for a role of phosphodiesterase 4 in lipopolysaccharide-stimulated prostaglandin E2 production and matrix metalloproteinase-9 activity in human amniochorionic membranes

Author

Céline Méhats, Stéphanie Oger, Emmanuelle Dallot, Marie-Josèphe Leroy, Dominique Cabrol, Développement humain : Croissance et différenciation, Institut des sciences du Médicament -Toxicologie - Chimie - Environnement (IFR71), Institut National de la Santé et de la Recherche Médicale (INSERM)-Ecole Nationale Supérieure de Chimie de Paris - Chimie ParisTech-PSL (ENSCP), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Ecole Nationale Supérieure de Chimie de Paris - Chimie ParisTech-PSL (ENSCP), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD)-Université Paris Descartes - Paris 5 (UPD5)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Leroy, Marie Josèphe, Institut de Recherche pour le Développement (IRD)-Ecole Nationale Supérieure de Chimie de Paris - Chimie ParisTech-PSL (ENSCP), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD)-Ecole Nationale Supérieure de Chimie de Paris - Chimie ParisTech-PSL (ENSCP), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), and Institut National de la Santé et de la Recherche Médicale (INSERM) - Ecole Nationale Supérieure de Chimie de Paris- Chimie ParisTech-PSL (ENSCP) - Centre National de la Recherche Scientifique (CNRS) - Institut de Recherche pour le Développement (IRD) - Université Paris Descartes - Paris 5 (UPD5) - Institut National de la Santé et de la Recherche Médicale (INSERM) - Ecole Nationale Supérieure de Chimie de Paris- Chimie ParisTech-PSL (ENSCP) - Centre National de la Recherche Scientifique (CNRS) - Institut de Recherche pour le Développement (IRD) - Université Paris Descartes - Paris 5 (UPD5) - Université Paris Descartes - Paris 5 (UPD5) - Institut National de la Santé et de la Recherche Médicale (INSERM)

Subjects
MESH : Phosphodiesterase Inhibitors, medicine.medical_treatment, MESH: Adjuvants, Immunologic, Matrix metalloproteinase, MESH : Tissue Culture Techniques, MESH: Enzyme Precursors, MESH : Immune Sera, 0302 clinical medicine, MESH: Pregnancy, Pregnancy, MESH: Up-Regulation, MESH: Immune Sera, MESH : Up-Regulation, 0303 health sciences, 030219 obstetrics & reproductive medicine, MESH : Cyclic AMP, MESH: Dinoprostone, Phosphodiesterase, Chorion, Up-Regulation, 3. Good health, Cell biology, MESH: Membrane Proteins, medicine.medical_specialty, MESH: Enzyme Activation, MESH : Cyclooxygenase 2, Immunology, MESH: Prostaglandin-Endoperoxide Synthases, MESH: Chorion, Dinoprostone, Proinflammatory cytokine, 03 medical and health sciences, Adjuvants, Immunologic, MESH : 3',5'-Cyclic-Nucleotide Phosphodiesterase, Humans, Amnion, MESH: Humans, Tumor Necrosis Factor-alpha, Immune Sera, MESH : Humans, Cilomilast, MESH: Matrix Metalloproteinase 9, Enzyme Activation, MESH : Pregnancy, Endocrinology, MESH : Rolipram, chemistry, MESH : Membrane Proteins, 3',5'-Cyclic-AMP Phosphodiesterases, MESH: Tumor Necrosis Factor-alpha, MESH: Lipopolysaccharides, MESH: Female, Lipopolysaccharides, MESH: Interleukin-10, Lipopolysaccharide, Phosphodiesterase Inhibitors, MESH : Lipopolysaccharides, MESH: Phosphodiesterase Inhibitors, Tissue Culture Techniques, chemistry.chemical_compound, MESH: Rolipram, Cyclic AMP, Immunology and Allergy, MESH : Female, MESH : Matrix Metalloproteinase 9, Prostaglandin E2, MESH: Cyclic AMP, MESH : Tumor Necrosis Factor-alpha, Enzyme Precursors, MESH : Prostaglandin-Endoperoxide Synthases, MESH : Enzyme Precursors, Interleukin-10, Cytokine, Matrix Metalloproteinase 9, MESH : Amnion, Female, MESH: Cyclooxygenase 2, Rolipram, medicine.drug, MESH : Dinoprostone, MESH: 3',5'-Cyclic-Nucleotide Phosphodiesterase, Biology, [SDV.MHEP.GEO]Life Sciences [q-bio]/Human health and pathology/Gynecology and obstetrics, MESH : Interleukin-10, Internal medicine, medicine, MESH: Tissue Culture Techniques, MESH: Amnion, 030304 developmental biology, Membrane Proteins, Cyclic Nucleotide Phosphodiesterases, Type 4, [SDV.MHEP.GEO] Life Sciences [q-bio]/Human health and pathology/Gynecology and obstetrics, MESH : Chorion, Cyclooxygenase 2, Prostaglandin-Endoperoxide Synthases, MESH : Adjuvants, Immunologic, MESH : Enzyme Activation
Abstract

Chorioamniotic infection is a leading cause of preterm premature rupture of fetal membranes (amnion and chorion). Bacterial infection induces an inflammatory response characterized by elevated production of proinflammatory cytokines; the latter activate the production of both PGs that stimulate uterine contractions, and matrix metalloproteinases (MMPs) that degrade the extracellular matrix of the chorioamniotic membranes. The inflammatory response is under the control of cAMP content, which is partly regulated by phosphodiesterases (PDE). In this study, we investigated the role of the PDE4 family in the inflammatory process triggered by LPS in a model of amniochorionic explants. We found that PDE4 family is the major cAMP-PDE expressed in human fetal membranes and that PDE4 activity is increased by LPS treatment. Selective inhibition of PDE4 activity affected LPS signaling, because PDE4 inhibitors (rolipram and/or cilomilast) reduced the release of the proinflammatory cytokine TNF-α and increased the release of the anti-inflammatory cytokine IL-10. PDE4 inhibition reduced cyclooxygenase-2 protein expression and PGE2 production and also modulated MMP-9, a key mediator of the membrane rupture process, by inhibiting pro-MMP-9 mRNA expression and pro-MMP-9 activity. These results demonstrate that the PDE4 family participates in the regulation of the inflammatory response associated with fetal membrane rupture during infection. The PDE4 family may be an appropriate pharmacological target for the management of infection-induced preterm delivery.

Published
2005

18. Distinct roles for retinoic acid receptors alpha and beta in early lung morphogenesis

Author

Tushar J. Desai, Pierre Chambon, Felicia Chen, Jun Qian, Jining Lu, Wellington V. Cardoso, Pascal Dollé, Karen Niederreither, Institut de génétique et biologie moléculaire et cellulaire (IGBMC), Université Louis Pasteur - Strasbourg I-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), and Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Louis Pasteur - Strasbourg I

Subjects
MESH: Aldehyde Oxidoreductases, MESH: Signal Transduction, Receptors, Retinoic Acid, Organogenesis, Retinoic acid, Fibroblast growth factor, MESH: Mice, Knockout, Tissue Culture Techniques, Mice, chemistry.chemical_compound, 0302 clinical medicine, Morphogenesis, MESH: Animals, Receptor, Lung, Mice, Knockout, 0303 health sciences, SftpC, Retinoic Acid Receptor alpha, Endoderm, Foregut, Cell Differentiation, respiratory system, Aldehyde Oxidoreductases, Cell biology, MESH: Endoderm, Nkx2.1, embryonic structures, Lung development, Lung morphogenesis, Signal Transduction, MESH: Cell Differentiation, Alpha (ethology), Biology, Cell fate determination, 03 medical and health sciences, Raldh2, Animals, MESH: Lung, MESH: Tissue Culture Techniques, Molecular Biology, MESH: Mice, 030304 developmental biology, MESH: Receptors, Retinoic Acid, FGF10, Fgf10, Endodermal specification, [SDV.BBM.BM]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Molecular biology, Cell Biology, MESH: Morphogenesis, chemistry, Immunology, MESH: Fibroblast Growth Factor 10, Fibroblast Growth Factor 10, 030217 neurology & neurosurgery, RAR, Developmental Biology
Abstract

International audience; Retinoic acid (RA) signaling is required for normal development of multiple organs. However, little is known about how RA influences the initial stages of lung development. Here, we used a combination of genetic, pharmacological and explant culture approaches to address this issue, and to investigate how signaling by different RA receptors (RAR) mediates the RA effects. We analyzed initiation of lung development in retinaldehyde dehydrogenase-2 (Raldh2) null mice, a model in which RA signaling is absent from the foregut from its earliest developmental stages. We provide evidence that RA is dispensable for specification of lung cell fate in the endoderm. By using synthetic retinoids to selectively activate RAR alpha or beta signaling in this model, we demonstrate novel and unique functions of these receptors in the early lung. We show that activation of RAR beta, but not alpha, induces expression of the fibroblast growth factor Fgf10 and bud morphogenesis in the lung field. Similar analysis of wild type foregut shows that endogenous RAR alpha activity is required to maintain overall RA signaling, and to refine the RAR beta effects in the lung field. Our data support the idea that balanced activation of RAR alpha and beta is critical for proper lung bud initiation and endodermal differentiation.

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