Hepatic mitochondrial transport of glutathione: studies in isolated rat liver mitochondria and H4IIE rat hepatoma cells.

Hepatic mitochondrial transport of glutathione: studies in isolated rat liver mitochondria and H4IIE rat hepatoma cells.
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谷胱甘肽的肝线粒体转运:离体大鼠肝线粒体和 H4IIE 大鼠肝癌细胞的研究。

DOI:
10.1016/j.abb.2008.03.008
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发表时间:
2008
影响因子:
3.9
通讯作者:
Lash,LawrenceH
Lash,LawrenceH
中科院分区:
生物学3区
文献类型:
--
作者:
Zhong,Qing;Putt,DavidA;Xu,Feng;Lash,LawrenceH

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谷胱甘肽(GSH)通过二羧酸盐(DIC;Slc25a10)和2-氧戊二酸载体(OGC;Slc25a11)转运到肾脏线粒体。为了确定这些载体在肝线粒体中的功能是否相似,我们评估了与特定底物或抑制剂竞争对分离的大鼠肝线粒体GSH摄取的影响。GSH摄取是单相的,不依赖于三磷酸腺苷的降解,每毫克蛋白的摄取值分别为4.08 mM和3.06 nmoL/min。与丙二酸丁酯和丁二酸苯酯孵育可抑制GSH摄取45-50%,尽管单独的抑制剂没有作用,这表明在大鼠肝线粒体中,DIC和OGC只对GSH摄取起部分作用。大鼠肝癌细胞株H4IIE稳定地转导OGC基因,GSH和2-羟基戊二酸摄取增加,并能抵抗H_2O_2、甲基乙烯基酮或顺铂诱导的细胞毒性,证实了线粒体GSH转运增加在肝脏中的保护作用。
Glutathione (GSH) is transported into renal mitochondria by the dicarboxylate (DIC; Slc25a10) and 2-oxoglutarate carriers (OGC; Slc25a11). To determine whether these carriers function similarly in liver mitochondria, we assessed the effect of competition with specific substrates or inhibitors on GSH uptake in isolated rat liver mitochondria. GSH uptake was uniphasic, independent of ATP hydrolysis, and exhibited Kmand Vmaxvalues of 4.08mM and 3.06nmol/min per mg protein, respectively. Incubation with butylmalonate and phenylsuccinate inhibited GSH uptake by 45–50%, although the individual inhibitors had no effect, suggesting in rat liver mitochondria, the DIC and OGC are only partially responsible for GSH uptake. H4IIE cells, a rat hepatoma cell line, were stably transfected with the cDNA for the OGC, and exhibited increased uptake of GSH and 2-oxoglutarate and were protected from cytotoxicity induced by H2O2, methyl vinyl ketone, or cisplatin, demonstrating the protective function of increased mitochondrial GSH transport in the liver.
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