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

基于镉动力学分析镉肾病发病机制

• 批准号: 17590106
• 负责人: TOSHIAKI Shibasaki
• 金额: $ 2.43万
• 依托单位: Kyoritsu University of Pharmacy
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2005
• 资助国家: 日本
• 起止时间: 2005 至 2007
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-17590106/
• 关键词: environment; heavy metals; kidney; toxicology

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.

二价金属转运蛋白1 （DMT1）是哺乳动物铁（Fe）转运蛋白，在体外也可转运镉（Cd）。本研究比较了DMT1功能失调的MK/Rej-mk/ MK小鼠（MK/ MK小鼠）和DMT1功能失调的缺铁野生型（WT）小鼠的Cd吸收，以阐明DMT1在体内肠道Cd吸收中的作用。以1 ppm的CdCl_2水溶液灌胃2周，测定小鼠肝、肾、肠上皮组织中Cd、Fe的浓度。WT小鼠肠上皮铁浓度随饲粮限铁水平成比例降低，而Cd积累在相同条件下增加。缺铁WT小鼠小肠DMT1 mRNA表达明显高于富铁WT小鼠。缺铁导致缺铁WT小鼠肠道Cd摄取上调。mk/mk小鼠的DMT1发生突变，其功能丧失导致肠道铁浓度下降。然而，肠道Cd积累与WT小鼠相同，缺铁情况下也增加了。可能存在一种未知的Cd途径在体内对Cd的肠道吸收起作用，并且该途径受食物铁浓度的调节。因此，DMT1并不是体内肠道镉吸收的唯一转运体。