U373-MG response to interleukin-1beta-induced oxidative stress.
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.
Malaplate-Armand
C
C
Centre du Médicament, UPRES 3117, Faculté de Pharmacie, Université Henri Poincaré, Nancy, France.
Gueguen
Y
Y
Bertrand
P
P
Ferrari
L
L
Batt
A M
AM
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
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