title: U373-MG response to interleukin-1beta-induced oxidative stress.
abstract: Oxidative stress has been involved in various neurological disorders and, in the central nervous system, astrocytes represent the cell type that contributes to neuroprotection via glutathione (GSH) metabolism, GSH-metabolizing enzymes like gamma-glutamyltransferase (GGT), and apoE secretion. In this study, using IL-1beta, a proinflammatory and prooxidant cytokine that is increased in numerous pathological situations, cells of astrocytoma cell line U373-MG were exposed to an oxidative stress, leading to c-Jun and c-Fos activation. IL-1beta decreased both GGT activity and intracellular GSH content and increased apoE secretion, initiating astroglial response to injury. We observed that antioxidants inhibit IL-1beta effects on c-Jun and c-Fos proteins, GGT activity and the GSH pool but not on apoE secretion. Our results allow us to conclude that neurological disorders associated with an IL-1beta-induced oxidative stress could be, at least experimentally, reversible in the presence of one antioxidant, N-acetylcysteine.
authors.affiliation: Centre du Médicament, UPRES 3117, Faculté de Pharmacie, Université Henri Poincaré, Nancy, France.
authors.forename: C
authors.initials: C
authors.lastname: Malaplate-Armand
authors.forename: Y
authors.initials: Y
authors.lastname: Gueguen
authors.forename: P
authors.initials: P
authors.lastname: Bertrand
authors.forename: L
authors.initials: L
authors.lastname: Ferrari
authors.forename: A M
authors.initials: AM
authors.lastname: Batt
mesh_terms: D000111:Acetylcysteine / Q000494:pharmacology; D001057:Apolipoproteins E / Q000378:metabolism; D001205:Ascorbic Acid / Q000494:pharmacology; D001254:Astrocytoma; D015153:Blotting, Western; D002470:Cell Survival; D004305:Dose-Response Relationship, Drug; D004789:Enzyme Activation / Q000187:drug effects; D016166:Free Radical Scavengers / Q000494:pharmacology; D005978:Glutathione / Q000378:metabolism; D006801:Humans; D007375:Interleukin-1 / Q000494:pharmacology*; D018384:Oxidative Stress / Q000187:drug effects / Q000502:physiology*; D016760:Proto-Oncogene Proteins c-fos / Q000032:analysis; D016755:Proto-Oncogene Proteins c-jun / Q000032:analysis; D014407:Tumor Cells, Cultured / Q000187:drug effects / Q000201:enzymology; D014810:Vitamin E / Q000494:pharmacology; D005723:gamma-Glutamyltransferase / Q000378:metabolism
chemical_list: D001057:Apolipoproteins E; D016166:Free Radical Scavengers; D007375:Interleukin-1; D016760:Proto-Oncogene Proteins c-fos; D016755:Proto-Oncogene Proteins c-jun; D014810:Vitamin E; D005723:gamma-Glutamyltransferase; D005978:Glutathione; D001205:Ascorbic Acid; D000111:Acetylcysteine