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4 results on '"MESH : Astrocytes"'

1. Effect of oxidative stress on UDP-glucuronosyltransferases in rat astrocytes

Author

Alain Minn, Daniela Gradinaru, Jean-Marie Heydel, Anne-Laure Minn, Yves Artur, University of Medicine and Pharmacy, Carol Davila University, Centre des Sciences du Goût et de l'Alimentation [Dijon] (CSGA), Institut National de la Recherche Agronomique (INRA)-Université de Bourgogne (UB)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Centre National de la Recherche Scientifique (CNRS), Physiopathologie, Pharmacologie et Ingénierie articulaires (PPIA), Université Henri Poincaré - Nancy 1 (UHP)-Centre National de la Recherche Scientifique (CNRS), Conseil Regional de Bourgogne, Dijon, France, EU-COST Action on Chemistry of Non-Enzymatic Protein Modifications [CM1001], Centre des Sciences du Goût et de l'Alimentation [Dijon] ( CSGA ), Institut National de la Recherche Agronomique ( INRA ) -Université de Bourgogne ( UB ) -AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Centre National de la Recherche Scientifique ( CNRS ), Laboratoire de Pharmacologie, and Université de Vandœuvre-lès-Nancy

Subjects
MESH : Oxidative Stress, MESH : RNA, Messenger, Antioxidant, Transcription, Genetic, medicine.medical_treatment, Toxicology, NAD(P)H:quinone oxidoreductase 1, MESH: Glucuronosyltransferase, Antioxidants, Substrate Specificity, Rats, Sprague-Dawley, 0302 clinical medicine, MESH: NADPH-Ferrihemoprotein Reductase, MESH: Glucuronides, NAD(P)H Dehydrogenase (Quinone), MESH : Catalysis, MESH: Animals, MESH : NAD(P)H Dehydrogenase (Quinone), Glucuronosyltransferase, Cells, Cultured, chemistry.chemical_classification, MESH : Cell Survival, 0303 health sciences, MESH : Substrate Specificity, MESH : Animals, Newborn, Cytochrome P450 reductase, General Medicine, MESH: Cell Survival, MESH: Pyridinium Compounds, MESH : Antioxidants, MESH: Cells, Cultured, Oxidative phosphorylation, Gene Expression Regulation, Enzymologic, MESH : Quinones, MESH : Glucuronides, 03 medical and health sciences, RNA, Messenger, Cell Shape, NADPH-Ferrihemoprotein Reductase, MESH : Oxidation-Reduction, MESH : Pyridinium Compounds, MESH: Naphthols, MESH : Glucuronosyltransferase, MESH: Antioxidants, MESH: Catalysis, chemistry, Oxidative stress, Astrocytes, Reactive Oxygen Species, 030217 neurology & neurosurgery, MESH: Oxidation-Reduction, Time Factors, [ SDV.AEN ] Life Sciences [q-bio]/Food and Nutrition, MESH : Reactive Oxygen Species, NADPH:cytochrome P450 reductase, Pyridinium Compounds, Naphthols, MESH: Rats, Sprague-Dawley, Protein oxidation, medicine.disease_cause, MESH: Animals, Newborn, MESH: NAD(P)H Dehydrogenase (Quinone), Protein Carbonylation, MESH : Oxidants, MESH: Oxidants, Melatonin, MESH: Melatonin, MESH: Oxidative Stress, MESH : Melatonin, MESH : Rats, MESH: Gene Expression Regulation, Enzymologic, Quinones, MESH: Reactive Oxygen Species, Oxidants, Biochemistry, MESH : Protein Carbonylation, Oxidation-Reduction, UDP-glucuronosyltransferase, MESH : Time Factors, MESH: Protein Carbonylation, MESH: Rats, Cell Survival, MESH : Naphthols, Biology, Catalysis, MESH: Quinones, MESH : Gene Expression Regulation, Enzymologic, Glucuronides, MESH : Cells, Cultured, medicine, Animals, MESH: Cell Shape, 030304 developmental biology, MESH: RNA, Messenger, Reactive oxygen species, MESH: Transcription, Genetic, MESH: Time Factors, MESH : Astrocytes, MESH : Transcription, Genetic, MESH : Rats, Sprague-Dawley, Rats, MESH: Astrocytes, Animals, Newborn, MESH : NADPH-Ferrihemoprotein Reductase, MESH: Substrate Specificity, MESH : Animals, NAD+ kinase, MESH : Cell Shape, [SDV.AEN]Life Sciences [q-bio]/Food and Nutrition
Abstract

WOS:000309170300003; International audience; The present work reports data regarding effects of an induced oxidative stress on the mainly expressed isoforms of UDP-glucuronosyltransferases (UGTs) in the brain. UGT1A6 and UGT1A7 expression and enzymatic activities toward the 1-naphthol were analyzed in rat cultured astrocytes following the exposure for 48 h to redox-cycling xenobiotic compounds such as quinones and bipyridinium ions. The expression of NADPH:cytochrome P450 reductase and NAD(P)H:quinone oxidoreductase 1 (NQO1) was also investigated. Oxidative stress induced significant deleterious changes in astrocyte morphology, decreased cell viability and inhibited catalytic function of UGTs as a result of protein oxidation. Alternatively, in the surviving impaired astrocytes, oxidative conditions induced a significant overactivity and overexpression of xenobiotic detoxification enzymes, as adaptive response. These effects were significantly prevented by the presence of melatonin, suggesting its direct antioxidant action on reactive oxygen species, reflected further on the glucuronidation activity and transcriptional regulation of both UGT1A6 and UGT1A7. Results show that both catalytic properties of UGTs and the expression of UGT1A6, UGT1A7, NQO1 and NADPH:cytochrome P450 reductase in rat astrocytes are greatly influenced by the pro-oxidative environment. In conclusion, an experimental increase in oxidative cellular status could have both immediate and long term consequences on detoxification enzymatic system activity and expression.

Published
2012
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2. Cell-penetrating anti-GFAP VHH and corresponding fluorescent fusion protein VHH-GFP spontaneously cross the blood-brain barrier and specifically recognize astrocytes: application to brain imaging

Author

Jean-Pierre Bourgeois, Anne-Marie Le Sourd, Fabienne Glacial, Pierre Lafaye, Susanna Celli, Pierre-Olivier Couraud, Babette B. Weksler, Ignacio A. Romero, Tengfei Li, Salah Mecheri, François Rougeon, Production de Protéines Recombinantes et d'Anticorps (Plate-Forme), Institut Pasteur [Paris] (IP), Gènes, Synapses et Cognition (CNRS - UMR3571 ), Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS), Institut National de la Santé et de la Recherche Médicale (INSERM), 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), Biologie des Interactions Hôte-Parasite, Division of Hematology and Oncology, Weill Medical College of Cornell University [New York], Department of Life, Health and Chemical Sciences, The Open University [Milton Keynes] (OU), Génétique et Biochimie du Développement, Institut Pasteur [Paris], Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS), Centre National de la Recherche Scientifique (CNRS)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre National de la Recherche Scientifique (CNRS)-Institut Pasteur [Paris], Gènes, Synapses et Cognition, Institut Pasteur [Paris]-Université Paris Diderot - Paris 7 ( UPD7 ) -Centre National de la Recherche Scientifique ( CNRS ), Institut National de la Santé et de la Recherche Médicale ( INSERM ), Institut Cochin ( UM3 (UMR 8104 / U1016) ), Université Paris Descartes - Paris 5 ( UPD5 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ), Institut Pasteur [Paris]-Centre National de la Recherche Scientifique ( CNRS ), and The Open University [Milton Keynes] ( OU )

Subjects
MESH : Cell Line, [SDV.IB.IMA]Life Sciences [q-bio]/Bioengineering/Imaging, Plasmodium berghei, MESH : Immunohistochemistry, [SDV.NEU.NB]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Neurobiology, Fluorescent Antibody Technique, Biochemistry, law.invention, Green fluorescent protein, MESH : Blood-Brain Barrier, MESH: Blood-Brain Barrier, Mice, 0302 clinical medicine, law, MESH: Glial Fibrillary Acidic Protein, MESH : Female, MESH: Animals, MESH: Fluorescent Antibody Technique, [ SDV.IB.IMA ] Life Sciences [q-bio]/Bioengineering/Imaging, 0303 health sciences, biology, Glial fibrillary acidic protein, intrabodies, MESH: Enzyme-Linked Immunosorbent Assay, Brain, MESH : Enzyme-Linked Immunosorbent Assay, MESH : Glial Fibrillary Acidic Protein, Immunohistochemistry, nanobodies, MESH : Mutagenesis, Site-Directed, 3. Good health, MESH: Mutagenesis, Site-Directed, medicine.anatomical_structure, Blood-Brain Barrier, [ SDV.NEU.NB ] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Neurobiology, MESH : Single-Domain Antibodies, Recombinant DNA, Female, Antibody, Biotechnology, MESH: Cell Line, Tumor, MESH : Recombinant Fusion Proteins, Recombinant Fusion Proteins, [ SDV.IMM.IMM ] Life Sciences [q-bio]/Immunology/Immunotherapy, fluobodies, Enzyme-Linked Immunosorbent Assay, MESH : Mice, Inbred C57BL, Astrocytoma, Blood–brain barrier, MESH: Single-Domain Antibodies, camelids, Cell Line, 03 medical and health sciences, MESH: Brain, Antigen, MESH: Mice, Inbred C57BL, Cell Line, Tumor, MESH : Mice, Glial Fibrillary Acidic Protein, Genetics, medicine, MESH: Recombinant Fusion Proteins, MESH: Plasmodium berghei, Animals, Humans, Molecular Biology, MESH: Mice, MESH : Plasmodium berghei, 030304 developmental biology, MESH: Humans, MESH : Cell Line, Tumor, MESH : Humans, MESH : Astrocytes, MESH : Astrocytoma, MESH: Immunohistochemistry, [SDV.IMM.IMM]Life Sciences [q-bio]/Immunology/Immunotherapy, Single-Domain Antibodies, central nervous system, Fusion protein, Molecular biology, MESH: Cell Line, MESH: Astrocytes, Mice, Inbred C57BL, MESH : Fluorescent Antibody Technique, MESH: Astrocytoma, MESH : Brain, Astrocytes, biology.protein, Mutagenesis, Site-Directed, Paratope, MESH : Animals, BBB, MESH: Female, 030217 neurology & neurosurgery
Abstract

International audience; Antibodies normally do not cross the blood-brain barrier (BBB) and cannot bind an intracellular cerebral antigen. We demonstrate here for the first time that a new class of antibodies can cross the BBB without treatment. Camelids produce native homodimeric heavy-chain antibodies, the paratope being composed of a single-variable domain called VHH. Here, we used recombinant VHH directed against human glial fibrillary acidic protein (GFAP), a specific marker of astrocytes. Only basic VHHs (e.g., pI=9.4) were able to cross the BBB in vitro (7.8 vs. 0% for VHH with pI=7.7). By intracarotid and intravenous injections into live mice, we showed that these basic VHHs are able to cross the BBB in vivo, diffuse into the brain tissue, penetrate into astrocytes, and specifically label GFAP. To analyze their ability to be used as a specific transporter, we then expressed a recombinant fusion protein VHH-green fluorescent protein (GFP). These "fluobodies" specifically labeled GFAP on murine brain sections, and a basic variant (pI=9.3) of the fusion protein VHH-GFP was able to cross the BBB and to label astrocytes in vivo. The potential of VHHs as diagnostic or therapeutic agents in the central nervous system now deserves attention.

Published
2012
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3. Differential erbB signaling in astrocytes from the cerebral cortex and the hypothalamus of the human brain.: ErbB signaling in human astrocytes

Author

Sharif, Ariane, Duhem-Tonnelle, Véronique, Allet, Cécile, Baroncini, Marc, Loyens, Anne, Kerr-Conte, Julie, Collier, Francis, Blond, Serge, Ojeda, Sergio, Junier, Marie-Pierre, Prévot, Vincent, Centre de Recherche Jean-Pierre AUBERT Neurosciences et Cancer - U1172 Inserm - U837 (JPArc), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Lille Nord de France (COMUE)-Université de Lille, Service de neurochirurgie, Hôpital Roger Salengro [Lille]-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Thérapie cellulaire du diabète, Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille, Droit et Santé, Service de gynécologie, Hôpital Jeanne de Flandre [Lille]-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Division of Neuroscience, Oregon Health and Science University [Portland] (OHSU)-Oregon National Primate Research Center (ONPRC), Oregon Health and Science University [Portland] (OHSU), Institut de psychiatrie et neurosciences (U894 / UMS 1266), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut National du Cancer, Agence National pour la Recherche, Fondation pour la Recherche Médicale, Association de Recherche contre le Cancer, NIH grants HD25123, U54 HD18185 and RR00163, Centre de Recherche Jean-Pierre AUBERT Neurosciences et Cancer - U837 (JPArc), Université Lille Nord de France (COMUE)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille, Centre de Psychiatrie et Neurosciences (U894), Centre de recherche Jean-Pierre Aubert-Neurosciences et Cancer, Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Université de Lille, Droit et Santé, Hôpital Roger Salengro-Centre Hospitalier Régional Universitaire [Lille] ( CHRU Lille ), Hôpital Jeanne de Flandre [Lille]-Centre Hospitalier Régional Universitaire [Lille] ( CHRU Lille ), Oregon National Primate Research Center-Oregon Health & Science University [Portland] ( OHSU ), Centre de Psychiatrie et Neurosciences ( CPN - U894 ), and Université Paris Descartes - Paris 5 ( UPD5 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM )

Subjects
growth factor, MESH : homo sapiens, MESH: epidermal growth factor, MESH: astrocytes, glial cells, neuron–glial interactions, MESH: neuroglia, MESH : epidermal growth factor, MESH : neuroglia, MESH : astrocytes, [ SDV.NEU ] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], MESH: homo sapiens, cerebral cortex, [SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], hypothalamus, skin and connective tissue diseases
Abstract

International audience; Studies in rodents have shown that astroglial erbB tyrosine kinase receptors are key regulatory elements in neuron-glia communication. Although both astrocytes and deregulation of erbB functions have been implicated in the pathogenesis of many common human brain disorders, erbB signaling in native human brain astrocytes has never been explored. Taking advantage of our ability to perform primary cultures from the cortex and the hypothalamus of human fetuses, we conducted a thorough analysis of erbB signaling in human astrocytes. We showed that human cortical astrocytes express erbB1, erbB2, and erbB3, whereas human hypothalamic astrocytes express erbB1, erbB2, and erbB4 receptors. Ligand-dependent activation of different erbB receptor heterodimeric complexes in these two populations of astrocytes translated into different morphological and proliferative responses. Although morphological plasticity was more pronounced in hypothalamic astrocytes than in cortical astrocytes, the former showed a lower mitogenic potential. Decreasing erbB4 expression via siRNA-mediated gene knockdown revealed that erbB4 constitutively restrains basal proliferative activity in hypothalamic astrocytes. We further show that treatment of human astrocytes with a protein kinase C activator results in rapid tyrosine phosphorylation of erbB receptors that involves cleavage of endogenous membrane bound erbB ligands by metalloproteinases. Together, these results indicate that erbB signaling in primary human brain astrocytes is functional, region-specific, and can be activated in a paracrine and/or autocrine manner. In addition, by revealing that some aspects of astroglial erbB signaling are different between human and rodents, our results provide a molecular framework to explore the potential involvement of astroglial erbB signaling deregulation in human brain disorders.

Published
2009
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4. Gestational vitamin B deficiency leads to homocysteine-associated brain apoptosis and alters neurobehavioral development in rats

Author

Emmanuelle Nédélec, Jean-Marc Alberto, Sébastien Blaise, Jean-Luc Daval, Jean-Louis Guéant, Carine Bossenmeyer-Pourié, Henri Schroeder, Développement et Communication Chimique chez les Insectes (DCCI), Centre National de la Recherche Scientifique (CNRS)-Université de Bourgogne (UB)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement, Unité de Recherches Animal et Fonctionnalités des Produits Animaux (URAFPA), Institut National de la Recherche Agronomique (INRA)-Université de Lorraine (UL), Nutrition-Génétique et Exposition aux Risques Environnementaux (NGERE), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL), Centre des Sciences du Goût et de l'Alimentation [Dijon] (CSGA), Institut National de la Recherche Agronomique (INRA)-Université de Bourgogne (UB)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Centre National de la Recherche Scientifique (CNRS), Université de Lorraine (UL)-Institut National de la Recherche Agronomique (INRA), Centre des Sciences du Goût et de l'Alimentation [Dijon] ( CSGA ), Institut National de la Recherche Agronomique ( INRA ) -Université de Bourgogne ( UB ) -AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Centre National de la Recherche Scientifique ( CNRS ), Développement et Communication Chimique chez les Insectes ( DCCI ), Centre National de la Recherche Scientifique ( CNRS ) -Université de Bourgogne ( UB ) -AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement, Unité de Recherches Animal et Fonctionnalités des Produits Animaux ( URAFPA ), Université de Lorraine ( UL ) -Institut National de la Recherche Agronomique ( INRA ), Nutrition-Génétique et Exposition aux Risques Environnementaux ( NGERE ), and Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Université de Lorraine ( UL )

Subjects
Time Factors, Homocysteine, [ SDV.AEN ] Life Sciences [q-bio]/Food and Nutrition, MESH: Neurons, MESH: Vitamin B Deficiency, Hippocampus, Apoptosis, MESH : Behavior, Animal, MESH : Maze Learning, chemistry.chemical_compound, 0302 clinical medicine, MESH: Pregnancy, Vitamin B Deficiency, MESH : Homocysteine, Pregnancy, MESH: Behavior, Animal, MESH : Female, MESH: Animals, MESH: Memory, MESH: Tumor Suppressor Protein p53, Neurons, 2. Zero hunger, 0303 health sciences, Behavior, Animal, MESH : Rats, MESH : Memory, Brain, medicine.anatomical_structure, MESH: Hyperhomocysteinemia, MESH: Pregnancy Complications, Female, MESH : Time Factors, medicine.medical_specialty, Hyperhomocysteinemia, MESH: Rats, Offspring, Central nervous system, Subventricular zone, Biology, MESH : Rats, Wistar, MESH : Pregnancy Complications, MESH : Neurons, Pathology and Forensic Medicine, 03 medical and health sciences, MESH: Brain, Memory, Internal medicine, medicine, Animals, MESH: Homocysteine, MESH : Vitamin B Deficiency, Rats, Wistar, Maze Learning, 030304 developmental biology, MESH: Apoptosis, MESH: Maze Learning, MESH: Time Factors, MESH : Astrocytes, MESH: Rats, Wistar, medicine.disease, Rats, Pregnancy Complications, MESH: Astrocytes, MESH : Pregnancy, MESH : Tumor Suppressor Protein p53, B vitamins, Endocrinology, MESH : Brain, chemistry, Astrocytes, RAT, MESH : Animals, Righting reflex, Tumor Suppressor Protein p53, MESH: Female, [SDV.AEN]Life Sciences [q-bio]/Food and Nutrition, MESH : Apoptosis, 030217 neurology & neurosurgery, MESH : Hyperhomocysteinemia, Regular Articles
Abstract

International audience; Hyperhomocysteinemia has been identified as a risk factor for neurological disorders. To study the influence of early deficiency in nutritional determinants of hyperhomocysteinemia on the developing rat brain, dams were fed a standard diet or a diet lacking methyl groups during gestation and lactation. Homocysteinemia progressively increased in the offspring of the deficient group and at 21 days reached 13.3+/-3.7 micromol/L versus 6.8+/-0.3 micromol/L in controls. Homocysteine accumulated in both neurons and astrocytes of selective brain structures including the hippocampus, the cerebellum, the striatum, and the neurogenic subventricular zone. Most homocysteine-positive cells expressed p53 and displayed fragmented DNA indicative of apoptosis. Righting reflex and negative geotaxis revealed a delay in the onset of integration capacities in the deficient group. Between 19 and 21 days, a poorer success score was recorded in deficient animals in a locomotor coordination test. A switch to normal food after weaning allowed restoration of normal homocysteinemia. Nevertheless, at 80 days of age, the exploratory behavior in the elevated-plus maze and the learning and memory behavior in the eight-arm maze revealed that early vitamin B deprivation is associated with persistent functional disabilities, possibly resulting from the ensuing neurotoxic effects of homocysteine.

Published
2007
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