Dehydroepiandrosterone inhibits the death of immunostimulated rat C6 glioma cells deprived of glucose

Brain Res. 2001 Dec 20;922(2):267-75. doi: 10.1016/s0006-8993(01)03185-7.

Abstract

Pretreatment of interferon-gamma and lipopolysaccharides made C6 glioma cells highly vulnerable to glucose deprivation. Neither 12 h of glucose deprivation nor 2-day treatment with interferon-gamma (100 U/ml) and lipopolysaccharides (1 microg/ml) altered the viability of C6 glioma cells. However, significant death of immunostimulated C6 glioma cells was observed after 5 h of glucose deprivation. The augmented death was prevented by dehydroepiandrosterone (DHEA) treatment during immunostimulation, but not by DHEA treatment during glucose deprivation. DHEA reduced the rise in nitrotyrosine immunoreactivity, a marker of peroxynitrite, and superoxide production in glucose-deprived immunostimulated C6 glioma cells. DHEA, however, did not protect glucose-deprived C6 glioma cells from the exogenously produced peroxynitrite by 3-morpholinosydnonimine. Further, DHEA did not alter the production of total reactive oxygen species and nitric oxide in immunostimulated C6 glioma cells. Superoxide dismutase (SOD) and the synthetic SOD mimetic Mn(III)tetrakis (4-benzoic acid) porphyrin inhibited the death of glucose-deprived immunostimulated C6 glioma cells. In addition, a superoxide anion generator paraquat reversed the protective effect of DHEA on the augmented death. The data indicate that DHEA prevents the glucose deprivation-evoked augmented death by inhibiting the production of superoxide anion in immunostimulated C6 glioma cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adjuvants, Immunologic / metabolism
  • Adjuvants, Immunologic / pharmacology*
  • Animals
  • Astrocytes / drug effects*
  • Astrocytes / immunology
  • Astrocytes / metabolism
  • Brain / immunology
  • Brain / metabolism
  • Brain / physiopathology
  • Brain Ischemia / drug therapy*
  • Brain Ischemia / immunology
  • Brain Ischemia / metabolism
  • Cell Death / drug effects*
  • Cell Death / immunology
  • Cytokines / immunology
  • Cytokines / metabolism
  • Dehydroepiandrosterone / metabolism
  • Dehydroepiandrosterone / pharmacology*
  • Enzyme Inhibitors / pharmacology
  • Free Radical Scavengers / pharmacology
  • Glioma
  • Glucose / deficiency*
  • Herbicides / pharmacology
  • Humans
  • Interferon-gamma / pharmacology
  • Lipopolysaccharides / pharmacology
  • Metalloporphyrins / pharmacology
  • Molsidomine / analogs & derivatives*
  • Molsidomine / pharmacology
  • Neurons / drug effects
  • Neurons / immunology
  • Neurons / metabolism
  • Nitric Oxide / metabolism
  • Oxidative Stress / drug effects
  • Oxidative Stress / immunology*
  • Paraquat / pharmacology
  • Peroxynitrous Acid / metabolism
  • Superoxide Dismutase / pharmacology
  • Tumor Cells, Cultured
  • Tyrosine / analogs & derivatives*
  • Tyrosine / drug effects
  • Tyrosine / metabolism

Substances

  • Adjuvants, Immunologic
  • Cytokines
  • Enzyme Inhibitors
  • Free Radical Scavengers
  • Herbicides
  • Lipopolysaccharides
  • Metalloporphyrins
  • Peroxynitrous Acid
  • Nitric Oxide
  • 3-nitrotyrosine
  • Tyrosine
  • Dehydroepiandrosterone
  • linsidomine
  • tetrakis(N-methyl-4-pyridiniumyl)porphine manganese(III) complex
  • Interferon-gamma
  • Molsidomine
  • Superoxide Dismutase
  • Glucose
  • Paraquat