Voest E E, van Faassen E, van Asbeck B S, Neijt J P, Marx J J
University Hospital Utrecht, Department of Internal Medicine, The Netherlands.
Biochim Biophys Acta. 1992 Aug 12;1136(2):113-8. doi: 10.1016/0167-4889(92)90245-7.
Evidence is presented that the nitroxide free radical, TEMPO, at concentrations commonly used to prevent oxidative damage, increases the intracellular hydrogen peroxide concentration. To investigate the origin of this increased hydrogen peroxide concentration, we have incubated various human tumor cell lines with compounds interfering with the generation of active oxygen metabolites. Sodium azide, inhibitor of the respiratory chain, the iron-chelating agent desferrioxamine, superoxide dismutase and catalase had no effect on the hydrogen peroxide concentration. Metyrapone, inhibitor of the cytochrome P450 system, was demonstrated to decrease, but not completely prevent, the hydrogen peroxide production. N-ethylmaleimide, a sulphydryl-bond alkylating agent, was able to completely prevent the increased hydrogen peroxide production. We conclude that, by increasing the cellular hydrogen peroxide concentration, TEMPO exerts a pro-oxidant effect. This increase in hydrogen peroxide production seems to be mediated by the induction of oxidase activity in the cytochrome P450 system, but other cellular systems involved in electron transport may also play a role.
有证据表明，在通常用于防止氧化损伤的浓度下，氮氧自由基TEMPO会增加细胞内过氧化氢的浓度。为了研究这种过氧化氢浓度增加的来源，我们用干扰活性氧代谢产物生成的化合物孵育了各种人类肿瘤细胞系。呼吸链抑制剂叠氮化钠、铁螯合剂去铁胺、超氧化物歧化酶和过氧化氢酶对过氧化氢浓度没有影响。细胞色素P450系统抑制剂甲吡酮被证明可降低但不能完全阻止过氧化氢的产生。巯基烷基化剂N-乙基马来酰亚胺能够完全阻止过氧化氢产生的增加。我们得出结论，通过增加细胞内过氧化氢浓度，TEMPO发挥促氧化作用。过氧化氢产生的这种增加似乎是由细胞色素P450系统中氧化酶活性的诱导介导的，但参与电子传递的其他细胞系统也可能起作用。
