MENADIONE-INDUCED CYTO-TOXICITY IS ASSOCIATED WITH PROTEIN THIOL OXIDATION AND ALTERATION IN INTRACELLULAR CA-2+ HOMEOSTASIS
MENADIONE-INDUCED CYTO-TOXICITY IS ASSOCIATED WITH PROTEIN THIOL OXIDATION AND ALTERATION IN INTRACELLULAR CA-2+ HOMEOSTASIS
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DOI：
10.1016/0003-9861(84)90207-8
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发表时间：
1984-01-01
影响因子：
3.9
通讯作者：
ORRENIUS, S
中科院分区：
文献类型：
--
作者：
DIMONTE, D;BELLOMO, G;ORRENIUS, S
使用新鲜分离的大鼠肝细胞研究了甲萘醌代谢过程中细胞内巯基稳态改变的毒理学意义。观察到蛋白质巯基耗尽与细胞活力丧失之间存在严格的相关性。蛋白巯基的损失先于细胞死亡，并且在还原型谷胱甘肽水平降低的细胞中发生得更快。蛋白质巯基的消耗也与抑制细胞内Ca2+流出和干扰细胞内Ca2+稳态有关。有人提出，甲萘醌代谢诱导的氧化应激在离体肝细胞的可溶性和蛋白质硫醇的消耗的结果，后者的效果是至关重要的与扰动的Ca2+稳态和细胞活力的损失。
The toxicological implications of alterations in intracellular thiol homeostasis during menadione metabolism have been investigated using freshly isolated rat hepatocytes. A strict correlation between depletion of protein sulfhydryl groups and loss of cell viability was observed. Loss of protein thiols preceded cell death, and occurred more rapidly in cells with decreased levels of reduced glutathione. Depletion of protein thiols was also associated with inhibition of Ca2+efflux from the cells and perturbation of intracellular Ca2+homeostasis. It is proposed that the oxidative stress induced by menadione metabolism in isolated hepatocytes results in the depletion of both soluble and protein thiols, and that the latter effect is critically associated with a perturbation of Ca2+homeostasis and loss of cell viability.