Dehydroepiandrosterone inhibits the death of immunostimulated rat C6 glioma cells deprived of glucose.
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.
Shin
C Y
CY
Department of Pharmacology, College of Pharmacy, Seoul National University, San 56-1, Shillim-Dong, Kwanak-Gu, Seoul 151-742, South Korea.
Choi
J W
JW
Jang
E S
ES
Ju
C
C
Kim
W K
WK
Kim
H C
HC
Choi
C R
CR
Ko
K H
KH
D000276:Adjuvants, Immunologic / Q000378:metabolism / Q000494:pharmacology*; D000818:Animals; D001253:Astrocytes / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism; D001921:Brain / Q000276:immunology / Q000378:metabolism / Q000503:physiopathology; D002545:Brain Ischemia / Q000188:drug therapy* / Q000276:immunology / Q000378:metabolism; D016923:Cell Death / Q000187:drug effects* / Q000276:immunology; D016207:Cytokines / Q000276:immunology / Q000378:metabolism; D003687:Dehydroepiandrosterone / Q000378:metabolism / Q000494:pharmacology*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D016166:Free Radical Scavengers / Q000494:pharmacology; D005910:Glioma; D005947:Glucose / Q000172:deficiency*; D006540:Herbicides / Q000494:pharmacology; D006801:Humans; D007371:Interferon-gamma / Q000494:pharmacology; D008070:Lipopolysaccharides / Q000494:pharmacology; D008665:Metalloporphyrins / Q000494:pharmacology; D008981:Molsidomine / Q000031:analogs & derivatives* / Q000494:pharmacology; D009474:Neurons / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D009569:Nitric Oxide / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects / Q000276:immunology*; D010269:Paraquat / Q000494:pharmacology; D030421:Peroxynitrous Acid / Q000378:metabolism; D013482:Superoxide Dismutase / Q000494:pharmacology; D014407:Tumor Cells, Cultured; D014443:Tyrosine / Q000031:analogs & derivatives* / Q000187:drug effects / Q000378:metabolism
D000276:Adjuvants, Immunologic; D016207:Cytokines; D004791:Enzyme Inhibitors; D016166:Free Radical Scavengers; D006540:Herbicides; D008070:Lipopolysaccharides; D008665:Metalloporphyrins; D030421:Peroxynitrous Acid; D009569:Nitric Oxide; C002744:3-nitrotyrosine; D014443:Tyrosine; D003687:Dehydroepiandrosterone; C002385:linsidomine; C050950:tetrakis(N-methyl-4-pyridiniumyl)porphine manganese(III) complex; D007371:Interferon-gamma; D008981:Molsidomine; D013482:Superoxide Dismutase; D005947:Glucose; D010269:Paraquat