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亚硒酸盐诱导的分离线粒体中NAD(P)H氧化和钙释放:与体内毒性的关系。

Selenite-induced NAD(P)H oxidation and calcium release in isolated mitochondria: relationship to in vivo toxicity.

作者信息

Vlessis A A, Mela-Riker L

出版信息

Mol Pharmacol. 1987 Jun;31(6):643-6.

PMID:3600609
Abstract

The effects of selenite on the mitochondrial NAD(P)H/NAD(P) ratio and calcium pool are described. Small quantities of selenite can 1) oxidize mitochondrial NAD(P)H and 2) induce calcium release from isolated mitochondria. Reduced NAD(P)H within intact mitochondria was monitored kinetically using the wavelength pair, 340-375 nm. NAD(P)H oxidation rates at various concentrations of selenite were calculated. Mitochondria from older animals can oxidize NAD(P)H faster than those of younger animals; maximum selenite-induced oxidation rates correlate well with age of the animal in both kidney (r = 0.920) and liver (r = 0.839) mitochondria, the oxidation rates in the adult (liver 15.4, kidney 34.8 nmol/min/mg of protein) being 3-5 times the rates in the 1- to 2-day-old newborn (liver 2.8, kidney 10.3 nmol/min/mg protein). Calcium fluxes within mitochondrial suspensions were monitored kinetically using the calcium indicator, Arsenazo III, and the wavelength pair, 660-685 nm. Susceptibility to selenite-induced calcium release is age dependent, the mitochondria of older animals being more susceptible. Incubation time required to induce calcium release was 77 +/- 30 sec in the adult compared to 406 +/- 25 sec at the age of 0-4 days in the newborn. The bimodal toxic manifestations of selenite in vivo are discussed in view of the age-dependent differences in selenite metabolism at the cellular level.

摘要

本文描述了亚硒酸盐对线粒体NAD(P)H/NAD(P)比值和钙库的影响。少量亚硒酸盐可:1)氧化线粒体NAD(P)H;2)诱导分离的线粒体释放钙。利用340 - 375nm波长对,动态监测完整线粒体中还原型NAD(P)H。计算了不同浓度亚硒酸盐下NAD(P)H的氧化速率。老年动物的线粒体比幼年动物的线粒体氧化NAD(P)H更快;在肾脏(r = 0.920)和肝脏(r = 0.839)线粒体中,亚硒酸盐诱导的最大氧化速率与动物年龄密切相关,成年动物(肝脏15.4,肾脏34.8 nmol/min/mg蛋白质)的氧化速率是1 - 2日龄新生动物(肝脏2.8,肾脏10.3 nmol/min/mg蛋白质)的3 - 5倍。利用钙指示剂偶氮胂III和660 - 685nm波长对,动态监测线粒体悬浮液中的钙通量。亚硒酸盐诱导钙释放的敏感性与年龄有关,老年动物的线粒体更敏感。成年动物诱导钙释放所需的孵育时间为77±30秒,而新生动物0 - 4日龄时为406±25秒。鉴于细胞水平上亚硒酸盐代谢的年龄依赖性差异,讨论了亚硒酸盐在体内的双峰毒性表现。

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