Zinc-toxicity alters mitochondrial metabolism and leads to decreased ATP production in hepatocytes
Zinc-toxicity alters mitochondrial metabolism and leads to decreased ATP production in hepatocytes
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DOI：
10.1002/jat.1263
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发表时间：
2008-03-01
影响因子：
3.3
通讯作者：
Appanna, Vasu D.
中科院分区：
文献类型：
--
作者：
Lemire, Joseph;Mailloux, Ryan;Appanna, Vasu D.
尽管锌 (Zn) 是一种已知的环境毒物，但其对细胞能量产生机制的影响尚不清楚。本研究调查了这种二价金属对人肝细胞癌细胞 (HepG2) 氧化 ATP 生成网络的影响。与对照细胞相比，锌攻击的细胞含有更多的氧化蛋白质和脂质。 Zn 通过抑制乌头酸酶、α-酮戊二酸脱氢酶、NAD(+) 依赖性异柠檬酸脱氢酶、琥珀酸脱氢酶和细胞色素 C 氧化酶，严重阻碍线粒体功能。与对照细胞相比，接触 Zn 的细胞具有不同的线粒体代谢，并且产生的 ATP 显着减少。然而，异柠檬酸脱氢酶-NADP(+)依赖性的表达在用Zn处理的细胞中更为突出。因此，锌诱导的病理可能是由于线粒体无法有效产生能量造成的。版权所有 (c) 2007 John Wiley & Sons, Ltd.
Although zinc (Zn) is a known environmental toxicant, its impact on the cellular energy-producing machinery is not well established. This study investigated the influence of this divalent metal on the oxidative ATP producing network in human hepatocellular carcinoma (HepG2) cells. Zn-challenged cells contained more oxidized proteins and lipids compared with control cells. Zn severely impeded mitochondrial functions by inhibiting aconitase, a-ketoglutarate dehydrogenase, isocitrate dehydrogenase-NAD(+) dependent, succinate dehydrogenase and cytochrome C oxidase Zn-exposed cells had a disparate mitochondrial metabolism compared with the control cells and produced significantly less ATP. However, the expression of isocitrate dehydrogenase-NADP(+) dependent was more prominent in cells treated with Zn. Hence, Zn-induced pathologies may be due to the inability of the mitochondria to generate energy effectively. Copyright (c) 2007 John Wiley & Sons, Ltd.