The role of zinc transporters in cadmium and manganese transport in mammalian cells
The role of zinc transporters in cadmium and manganese transport in mammalian cells
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DOI：
10.1016/j.biochi.2009.04.002
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发表时间：
2009-10-01
期刊：
影响因子：
3.9
通讯作者：
Fujishiro, Hitomi
中科院分区：
文献类型：
--
作者：
Himeno, Seiichiro;Yanagiya, Takahiro;Fujishiro, Hitomi
为了了解镉的积累机制，了解其他金属的转运系统的确切机制是很重要的。近年来，基因组学和金属组学的应用已经阐明了特定金属转运体在镉吸收中的作用。对金属硫蛋白(MT)-零抗镉细胞的研究揭示了锰/锌转运系统参与镉吸收。菌株对镉诱导睾丸出血敏感性差异的基因组研究表明，slc39a8编码的锌转运蛋白Zrt- irt相关蛋白（ZIP） 8是造成菌株差异的原因。ZIP8在不同细胞中的异位表达增强了镉、锰和锌的摄取。ZIP8转基因小鼠在睾丸血管和肾近端小管顶端膜中高表达，镉对小鼠的镉积累和毒性增强。在MT-null抗镉细胞中，ZIP8的表达下调，对镉和锰的摄取速率均降低。这些数据表明，ZIP8在哺乳动物细胞对镉和锰的吸收中起重要作用。讨论了ZIP14在镉和锰吸收中的作用。(C) 2009 Elsevier Masson SAS。版权所有。
To understand the mechanism of cadmium accumulation, it is important to know the precise mechanisms of transport systems for other metals. Recently, utilization of genomics and metallomics has clarified the involvement of specific metal transporter(s) in cadmium uptake. Studies with metallothionein (MT)-null cadmium-resistant cells have revealed the involvement of the manganese/zinc transport system in cadmium uptake. Genomic studies of strain differences in sensitivity to cadmium-induced testicular hemorrhage revealed that a zinc transporter, Zrt-, Irt-related protein (ZIP) 8 encoded by slc39a8, is responsible for the strain difference. Ectopic expression of ZIP8 in various cells enhanced the uptake of cadmium, manganese, and zinc. ZIP8-transgenic mice showed high expression of ZIP8 in the vasculature of testis and apical membrane of proximal tubules in kidney, and exhibited enhanced cadmium accumulation and toxicity when treated with cadmium. The expression of ZIP8 was found to be down-regulated in MT-null cadmium-resistant cells, in which the uptake rates of both cadmium and manganese were decreased. These data suggest that ZIP8 plays an important role in the uptake of both cadmium and manganese in mammalian cells. The role of ZIP14 in the uptake of cadmium and manganese is also discussed. (C) 2009 Elsevier Masson SAS. All rights reserved.