Intestinal absorption of cadmium is associated with divalent metal transporter 1 in rats
Intestinal absorption of cadmium is associated with divalent metal transporter 1 in rats
复制标题
DOI：
10.1093/toxsci/68.2.288
复制
发表时间：
2002-08-01
影响因子：
3.8
通讯作者：
Klaassen, CD
中科院分区：
文献类型：
--
作者：
Park, JD;Cherrington, NJ;Klaassen, CD
当体内铁（Fe）储备耗尽时，肠道对镉（Cd）的吸收增加。铁耗竭上调二价金属转运蛋白1（DMT 1）的表达，DMT 1位于小肠上皮细胞的顶膜。DMT 1已被证明在体外转运Fe和其他二价金属离子。然而，目前尚不清楚DMT 1是否介导镉的肠道吸收。为了研究DMT 1参与镉吸收，大鼠喂养饮食4周，无论是缺乏铁（FeD饮食，2-6 mg Fe/kg）或补充铁（FeS饮食，120 mg Fe/kg），然后通过一个单一的口服给药109氯化镉。在镉给药后48 h测定体内铁状态、血红蛋白和组织镉浓度。此外，DMT 1 mRNA水平定量在十二指肠，肾脏和肝脏的分支DNA信号放大方法。喂食FeD饲料的动物表现出体重增加减少、体内铁消耗和缺铁性贫血。组织镉浓度显着高于FeS饮食喂养大鼠，特别是在十二指肠。镉保留在体内的量是10倍高，在大鼠喂养的FeD饮食比那些喂养的FeS饮食。DMT 1 mRNA在十二指肠中高度表达，并且在FeD饮食组中高出15倍。DMT 1 mRNA的水平显着低于肾脏和肝脏比在十二指肠，但分别高出30和40%，在喂食FeD饮食的大鼠比在喂食FeS饮食的大鼠。这些研究结果表明，功能DMT 1蛋白可能是上调在小肠中的mRNA水平的身体铁耗竭，并增加镉的吸收从胃肠道与随后的镉转移到循环和身体组织。此外，本研究的数据可能表明DMT 1是一种非特异性的金属转运蛋白，它不仅可以转运Fe，而且可能也可以转运有毒金属。
The intestinal absorption of cadmium (Cd) increases when the body iron (Fe) stores are depleted. The depletion of Fe upregulates the expression of divalent metal transporter 1 (DMT1), which is located at the apical membrane of enterocytes lining the small intestine. DMT1 has been shown to transport Fe and other divalent metal ions in vitro. However, it is not known whether DMT1 mediates the intestinal absorption of Cd. To investigate DMT1 involvement in Cd absorption, rats were fed a diet for 4 weeks either deficient in Fe (FeD diet, 2-6 mg Fe/kg) or supplemented with Fe (FeS diet, 120 mg Fe/kg), followed by a single oral administration of 109 CdCl2. Body Fe status, hemoglobin, and tissue Cd concentration were determined at 48 h after Cd administration. Also, DMT1 mRNA levels were quantified in duodenum, kidney, and liver by the branched DNA signal amplification method. Animals fed the FeD diet exhibited a reduced body weight gain, depletion of body Fe, and Fe deficiency anemia. Tissue Cd concentration was significantly higher in FeD than in FeS diet-fed rats, especially in the duodenum. The amount of Cd retained in the body was 10-fold higher in rats fed the FeD diet than in those fed the FeS diet. DMT1 mRNA was highly expressed in duodenum and was 15-fold higher in the FeD diet group. The levels of DMT1 mRNA were significantly lower in kidney and liver than in duodenum, but were 30 and 40% higher, respectively, in rats fed the FeD diet than in rats fed the FeS diet. These findings suggest that functional DMT1 protein is likely upregulated in the small intestine at the mRNA level by body iron depletion and increases Cd uptake from the gastrointestinal tract with subsequent transfer of Cd to the circulation and body tissues. Furthermore, the data from this study may indicate that DMT1 is a nonspecific metal transporter, which can transport not only Fe, but probably the toxic metal as well.