U373-MG response to interleukin-1beta-induced oxidative stress.

C Malaplate-Armand, Y Gueguen, P Bertrand, L Ferrari, A M Batt

Journal: Cell biology and toxicology 2001;16(3):155-63

PMID: 11032359

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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.

Address: Centre du Médicament, UPRES 3117, Faculté de Pharmacie, Université Henri Poincaré, Nancy, France.

DOI: 10.1023/a:1007654804730

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MeSH Terms: Acetylcysteine, Apolipoproteins E, Ascorbic Acid, Astrocytoma, Blotting, Western, Cell Survival, Dose-Response Relationship, Drug, Enzyme Activation, Free Radical Scavengers, Glutathione, Humans, Interleukin-1, Oxidative Stress, Proto-Oncogene Proteins c-fos, Proto-Oncogene Proteins c-jun, Tumor Cells, Cultured, Vitamin E, gamma-Glutamyltransferase