Analysis of the mechanism of cadmium nephropathy based on, cadmium kinetics

二价金属转运蛋白1(DMT1)是哺乳动物铁(Fe)的转运蛋白，也是镉(Cd)的体外转运蛋白。本研究比较了DMT1功能障碍的MK/Rej-MK/MK小鼠(MK/MK小鼠)和DMT1功能缺陷的野生型(WT)小鼠对Cd的吸收，以阐明DMT1在体内肠道Cd吸收中的作用。小鼠饮水中加入1ppm的氯化镉AQ，连续2周，测定肝、肾、肠上皮中镉和铁的含量。WT小鼠肠道上皮细胞中铁含量随饲料铁限量水平的增加而降低，而Cd的积累量在相同条件下增加。与缺铁组相比，缺铁组小鼠小肠中DMT1mRNA的表达显著增加。缺铁引起WT小鼠肠道Cd摄取上调。MK/MK小鼠存在DMT1基因突变，其功能丧失导致肠道铁浓度降低。然而，在缺铁的情况下，小鼠肠道中Cd的蓄积量与WT小鼠相同，也增加。有可能是一种未知的镉途径在体内对镉的肠道吸收起了作用，并且这一途径受食物铁浓度的调节。因此，DMT1不是体内镉吸收的唯一转运体。

Divalent metal transporter 1 (DMT1) is a mammalian iron (Fe) transporter and also transports Cadmium (Cd) in vitro. This study compared Cd absorption in DMT1-dysfunctional MK/Rej-mk/mk mice (mk/mk mice) and in DMT1-functional, Fe-deficient wild-type (WT) mice, to clarify the role of DMT1 in intestinal Cd absorption in vivo. Mice were given 1 ppm CdCl_2 aq in drinking water for 2 weeks, and the concentrations of Cd and Fe in liver, kidney, and intestinal epithelium were subsequently determined. The Fe concentration in intestinal epithelia of WT mice was decreased in proportion to the level of dietary Fe limitation, while Cd accumulation under the same conditions was increased. DMT1 mRNA expression in the small intestine of Fe-deficient WT mice was dearly increased compared to that in Fe-sufficient WT mice. Iron deficiency resulted in upregulation of Cd uptake in the intestine of Fe-deficient WT mice. The mk/mk mice have a mutation in DMT1 and loss of its function led to decreased intestinal Fe concentration. However, intestinal Cd accumulation was the same as in WT mice and it was also increased in Fe-deficient situation. There is the possibility that an unknown Cd pathway has taken a role on Cd intestinal absorption in vivo and that this pathway is regulated by food Fe concentrations. Therefore, DMT1 is not the sole transporter of intestinal cadmium absorption in viva.