Renal organic cation transporters mediated cadmium-induced nephrotoxicity
Renal organic cation transporters mediated cadmium-induced nephrotoxicity
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DOI：
10.1016/j.toxlet.2011.04.005
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发表时间：
2011-07-04
影响因子：
3.5
通讯作者：
Chatsudthipong, Varanuj
中科院分区：
文献类型：
--
作者：
Soodvilai, Sunhapas;Nantavishit, Jiriporn;Chatsudthipong, Varanuj
在稳定转染兔（rb）OCT 1和rbOCT 2的中国仓鼠卵巢（CHO-K1）细胞、小鼠离体肾近曲小管和结扎双侧输尿管的大鼠完整肾脏中，研究了肾脏有机阳离子转运蛋白（OCTs）参与镉转运的情况。镉通过两种转运蛋白抑制rbOCT 1和rbOCT 2的底物[（3）H]-四乙基铵（TEA）的摄取，镉对rbOCT 1和rbOCT 2介导的TEA摄取的半数最大抑制浓度（IC（50））分别为96 +/- 5 μ M和207 +/- 12 μ M。在离体非灌注肾近端小管中，镉同样抑制[（3）H]-TEA摄取。转染CHO-K1细胞的镉蓄积量明显高于亲本细胞，TEA可使镉蓄积量降低。此外，镉在整个肾脏中的积累也减少了TEA的管理。此外，暴露的rbOCT 1和rbOCT 2表达CHO-K1细胞镉导致细胞毒性，这可以通过TEA治疗。总之，这项研究首次提供了证据，表明OCT 1和OCT 2介导镉转运穿过基底外侧膜进入肾近端小管细胞。(C)2011爱思唯尔爱尔兰有限公司保留所有权利。
The involvement of renal organic cation transporters (OCTs) in cadmium transport was investigated in Chinese hamster ovary (CHO-K1) cells stably and singly transfected with rabbit (rb)OCT1 and rbOCT2, in murine isolated renal proximal tubule, and in intact kidney following bilateral ureteral ligation of rat. Cadmium inhibited uptake of [(3)H]-tetraethylammonium (TEA), a substrate of rbOCT1 and rbOCT2, via both transporters with half maximal inhibitory concentration (IC(50)) of cadmium for rbOCT1- and rbOCT2-mediated TEA uptake of 96 +/- 5 mu M and 207 +/- 12 mu M, respectively. Cadmium similarly inhibited [(3)H]-TEA uptake in isolated non perfused renal proximal tubules. Cadmium accumulation in the transfected CHO-K1 cells was significantly higher than that of parent cells and this could be attenuated by TEA. In addition, cadmium accumulation in whole kidney was also reduced by TEA administration. Furthermore, exposure of the rbOCT1- and rbOCT2-expressing CHO-K1 cells to cadmium led to cytotoxicity, which could be prevented by TEA treatment. Taken together, this study provides for the first time, evidence showing OCT1 and OCT2 mediating cadmium transport across the basolateral membrane into the renal proximal tubular cells. (C) 2011 Elsevier Ireland Ltd. All rights reserved.