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

二价金属转运蛋白1（DMT 1）是哺乳动物铁转运蛋白，也是镉转运蛋白。本研究比较了DMT 1功能障碍的MK/Rej-RP 1/RP 2小鼠（RP 1/RP 2小鼠）和DMT 1功能障碍的铁缺乏野生型（WT）小鼠对镉的吸收，以阐明DMT 1在体内肠道镉吸收中的作用。用1 ppm的CdCl_2水溶液灌胃小鼠2周，然后测定肝、肾和肠上皮中Cd和Fe的浓度。WT小鼠肠上皮细胞中的铁浓度与铁限制水平成比例降低，而镉积累在相同条件下增加。与铁充足的WT小鼠相比，铁缺乏的WT小鼠小肠中的DMT 1 mRNA表达显著增加。铁缺乏导致铁缺乏WT小鼠肠道中镉吸收的上调。DMT 1基因突变导致小鼠肠道铁离子浓度降低。然而，肠道镉积累是相同的WT小鼠，它也增加了铁缺乏的情况。有一种可能性，一个未知的镉途径已经采取了镉在体内肠道吸收的作用，这条途径是由食物铁浓度调节。因此，DMT 1不是体内肠道镉吸收的唯一转运蛋白。

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.