NITRIC-OXIDE PROTECTS AGAINST CELLULAR-DAMAGE AND CYTOTOXICITY FROM REACTIVE OXYGEN SPECIES

被引:721
作者
WINK, DA
HANBAUER, I
KRISHNA, MC
DEGRAFF, W
GAMSON, J
MITCHELL, JB
机构
[1] NCI, RADIAT ONCOL BRANCH,RADIOL SECT,BLDG 10, ROOM B3-B69, BETHESDA, MD 20892 USA
[2] NCI, FREDERICK CANC RES & DEV CTR, CHEM SECT, COMPARAT CARCINOGENESIS LAB, FREDERICK, MD 21702 USA
[3] NHLBI, CHEM PHARMACOL LAB, BETHESDA, MD 20892 USA
关键词
D O I
10.1073/pnas.90.21.9813
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
Nitric oxide, NO, which is generated by various components of the immune system, has been presumed to be cytotoxic. However, NO has been proposed to be protective against cellular damage resulting during ischemia reperfusion. Along with NO there is often concomitant formation of superoxide/hydrogen peroxide, and hence a synergistic relationship between the cytotoxic effects of nitric oxide and these active oxygen species is frequently assumed. To study more carefully the potential synergy between NO and active oxygen species in mammalian cell cytotoxicity, we utilized either hypoxanthine/xanthine oxidase (a system that generates superoxide/hydrogen peroxide) or hydrogen peroxide itself. NO generation was accomplished by the use of a class of compounds known as ''NONOates,'' which release NO at ambient temperatures without the requirement of enzyme activation or biotransformation. When Chinese hamster lung fibroblasts (V79 cells) were exposed to hypoxanthine/xanthine oxidase for various times or increasing amounts of hydrogen peroxide, there was a dose-dependent decrease in survival of V79 cells as measured by clonogenic assays. However, in the presence of NO released from (C2H5)2N[N(O)NO]-Na+ (DEA/NO), the cytotoxicity resulting from superoxide or hydrogen peroxide was markedly abrogated. Similarly, primary cultures of rat mesencephalic dopaminergic cells exposed either to hydrogen peroxide or to hypoxanthine/xanthine oxidase resulted in the degradation of the dopamine uptake and release mechanism. As was observed in the case of the V79 cells, the presence of NO essentially abrogated this peroxide-mediated cytotoxic effect on mesencephalic cells.
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页码:9813 / 9817
页数:5
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