Struck A T, Hogg N, Thomas J P, Kalyanaraman B
Biophysics Research Institute, Medical College of Wisconsin, Milwaukee 53226.
FEBS Lett. 1995 Mar 20;361(2-3):291-4. doi: 10.1016/0014-5793(95)00178-c.
Photo-oxidized low-density lipoprotein is cytotoxic to bovine aortic endothelial cells in a concentration-dependent manner. Total cell killing occurs at a concentration of 600 mumol/l lipid hydroperoxide (LOOH). Selenium deficiency enhances the toxicity of LOOH such that 300 mumol/l LOOH is cytotoxic. This toxicity is inhibited by desferrioxamine, a transition metal ion chelator, and by butylatedhydroxytoluene, a potent inhibitor of lipid peroxidation. Toxicity is also inhibited by the nitric oxide donors S-nitrosoglutathione and spermine NONOate but not by reduced or oxidized glutathione and spermine. We propose that nitric oxide, released from these compounds, is inhibiting the toxicity of LOOH to selenium-deficient endothelial cells. Furthermore we hypothesize that the mechanism for this inhibition of toxicity is the scavenging of the propagatory peroxyl and alkoxyl free radicals, by nitric oxide, that are generated during peroxidation of cell membranes.
光氧化低密度脂蛋白对牛主动脉内皮细胞具有浓度依赖性细胞毒性。当脂质过氧化氢（LOOH）浓度达到600μmol/L时，可导致细胞全部死亡。硒缺乏会增强LOOH的毒性，使得300μmol/L的LOOH就具有细胞毒性。这种毒性可被去铁胺（一种过渡金属离子螯合剂）和丁基羟基甲苯（一种有效的脂质过氧化抑制剂）抑制。一氧化氮供体S-亚硝基谷胱甘肽和精胺亚硝基铁氰化物也可抑制毒性，但还原型或氧化型谷胱甘肽以及精胺则无此作用。我们认为，这些化合物释放的一氧化氮可抑制LOOH对缺硒内皮细胞的毒性。此外，我们推测这种毒性抑制机制是一氧化氮清除了细胞膜过氧化过程中产生的传播性过氧自由基和烷氧自由基。
