二价金属离子转运体1(DMT1)和锌铁转运蛋白14(ZIP14)在Caco-2细胞镉吸收中的浓度依赖性作用
Concentration-dependent roles of DMT1 and ZIP14 in cadmium absorption in Caco-2 cells.
作者信息
Fujishiro Hitomi, Hamao Satoko, Tanaka Rina, Kambe Taiho, Himeno Seiichiro
机构信息
Laboratory of Molecular Nutrition and Toxicology, Faculty of Pharmaceutical Sciences, Tokushima Bunri University.
Division of Integrated Life Science, Graduate School of Biostudies, Kyoto University.
出版信息
J Toxicol Sci. 2017;42(5):559-567. doi: 10.2131/jts.42.559.
Intestinal absorption of cadmium (Cd) is considered to be mediated mainly by the ferrous iron transporter DMT1, or the calcium transporter CaT1. The roles of zinc transporters such as ZIP8 and ZIP14 remain unclear, and the roles of these four transporters in the intestinal uptake of Cd under physiological conditions have not been compared. Here, we used a trans-well cell culture system to investigate the effects of the down-regulation of these four transporters on the uptake of Cd from the apical side of enterocytes. We used a Caco-2-kh cell line that can form tight junctions within a few days. The transfection of DMT1 siRNA significantly decreased the Cd uptake from the apical side at 5 μM, but not at 0.1 or 1 μM. The transfection of ZIP14 siRNA markedly decreased the Cd uptake at 0.1 and 1 μM, but not at 5 μM. The transfection of siRNA of CaT1 or ZIP8 did not alter the Cd uptake at any concentrations of Cd examined. These results suggest that DMT1 and ZIP14 play different roles in intestinal Cd absorption depending on the concentration of Cd.
镉(Cd)的肠道吸收被认为主要由亚铁离子转运蛋白DMT1或钙转运蛋白CaT1介导。锌转运蛋白如ZIP8和ZIP14的作用仍不清楚,且这四种转运蛋白在生理条件下对肠道摄取镉的作用尚未进行比较。在此,我们使用跨膜细胞培养系统来研究这四种转运蛋白的下调对肠细胞顶端侧摄取镉的影响。我们使用了一种Caco-2-kh细胞系,该细胞系可在数天内形成紧密连接。转染DMT1 siRNA显著降低了5 μM时从顶端侧摄取的镉,但在0.1或1 μM时未降低。转染ZIP14 siRNA显著降低了0.1和1 μM时的镉摄取,但在5 μM时未降低。转染CaT1或ZIP8的siRNA在任何检测的镉浓度下均未改变镉摄取。这些结果表明,DMT1和ZIP14在肠道镉吸收中根据镉的浓度发挥不同作用。