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
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Research Support, Non-U.S. Gov't
MeSH terms
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Adjuvants, Immunologic / metabolism
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Adjuvants, Immunologic / pharmacology*
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Animals
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Astrocytes / drug effects*
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Astrocytes / immunology
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Astrocytes / metabolism
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Brain / immunology
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Brain / metabolism
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Brain / physiopathology
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Brain Ischemia / drug therapy*
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Brain Ischemia / immunology
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Brain Ischemia / metabolism
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Cell Death / drug effects*
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Cell Death / immunology
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Cytokines / immunology
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Cytokines / metabolism
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Dehydroepiandrosterone / metabolism
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Dehydroepiandrosterone / pharmacology*
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Enzyme Inhibitors / pharmacology
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Free Radical Scavengers / pharmacology
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Glioma
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Glucose / deficiency*
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Herbicides / pharmacology
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Humans
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Interferon-gamma / pharmacology
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Lipopolysaccharides / pharmacology
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Metalloporphyrins / pharmacology
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Molsidomine / analogs & derivatives*
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Molsidomine / pharmacology
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Neurons / drug effects
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Neurons / immunology
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Neurons / metabolism
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Nitric Oxide / metabolism
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Oxidative Stress / drug effects
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Oxidative Stress / immunology*
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Paraquat / pharmacology
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Peroxynitrous Acid / metabolism
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Superoxide Dismutase / pharmacology
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Tumor Cells, Cultured
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Tyrosine / analogs & derivatives*
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Tyrosine / drug effects
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Tyrosine / metabolism
Substances
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Adjuvants, Immunologic
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Cytokines
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Enzyme Inhibitors
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Free Radical Scavengers
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Herbicides
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Lipopolysaccharides
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Metalloporphyrins
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Peroxynitrous Acid
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Nitric Oxide
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3-nitrotyrosine
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Tyrosine
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Dehydroepiandrosterone
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linsidomine
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tetrakis(N-methyl-4-pyridiniumyl)porphine manganese(III) complex
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Interferon-gamma
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Molsidomine
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Superoxide Dismutase
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Glucose
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Paraquat