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

Cell Biol Toxicol. 2000;16(3):155-63. doi: 10.1023/a:1007654804730.

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.

MeSH terms

  • Acetylcysteine / pharmacology
  • Apolipoproteins E / metabolism
  • Ascorbic Acid / pharmacology
  • Astrocytoma*
  • Blotting, Western
  • Cell Survival
  • Dose-Response Relationship, Drug
  • Enzyme Activation / drug effects
  • Free Radical Scavengers / pharmacology
  • Glutathione / metabolism
  • Humans
  • Interleukin-1 / pharmacology*
  • Oxidative Stress / drug effects
  • Oxidative Stress / physiology*
  • Proto-Oncogene Proteins c-fos / analysis
  • Proto-Oncogene Proteins c-jun / analysis
  • Tumor Cells, Cultured / drug effects
  • Tumor Cells, Cultured / enzymology
  • Vitamin E / pharmacology
  • gamma-Glutamyltransferase / metabolism

Substances

  • Apolipoproteins E
  • Free Radical Scavengers
  • Interleukin-1
  • Proto-Oncogene Proteins c-fos
  • Proto-Oncogene Proteins c-jun
  • Vitamin E
  • gamma-Glutamyltransferase
  • Glutathione
  • Ascorbic Acid
  • Acetylcysteine