Identification of SLC41A3 as a novel player in magnesium homeostasis.
Identification of SLC41A3 as a novel player in magnesium homeostasis.
复制标题
DOI：
10.1038/srep28565
复制
发表时间：
2016-06-28
影响因子：
4.6
通讯作者：
Hoenderop JG
中科院分区：
文献类型：
--
作者：
de Baaij JH;Arjona FJ;van den Brand M;Lavrijsen M;Lameris AL;Bindels RJ;Hoenderop JG
体内 Mg2+ 平衡的调节发生在远曲小管 (DCT)，其中跨细胞重吸收决定了最终的尿液 Mg2+ 排泄。 DCT 中基底外侧 Mg2+ 挤出机制尚不清楚，但最近的研究结果表明 SLC41 蛋白有助于 Mg2+ 挤出。因此，本研究的目的是使用 Slc41a3 敲除 (Slc41a3−/−) 小鼠来表征 SLC41A3 在 Mg2+ 稳态中的功能作用。通过定量PCR分析表明，Slc41a3是唯一在DCT中富集表达的SLC41亚型。有趣的是，血清和尿液电解质测定表明 Slc41a3−/− 小鼠患有低镁血症。使用低 Mg2+ 饮食喂养的小鼠中的稳定 25Mg2+ 同位素测量肠道 Mg2+ 吸收能力。野生型 (Slc41a3+/+) 和 Slc41a3−/− 小鼠中 25Mg2+ 的摄取相似，尽管 Slc41a3−/− 动物表现出 Mg2+ 转运蛋白 Trpm6 和 Slc41a1 肠道 mRNA 表达增加。值得注意的是，一些 Slc41a3−/− 小鼠出现了严重的单侧肾积水。总之，SLC41A3 被确立为 Mg2+ 处理的新因子。
Regulation of the body Mg2+ balance takes place in the distal convoluted tubule (DCT), where transcellular reabsorption determines the final urinary Mg2+ excretion. The basolateral Mg2+ extrusion mechanism in the DCT is still unknown, but recent findings suggest that SLC41 proteins contribute to Mg2+ extrusion. The aim of this study was, therefore, to characterize the functional role of SLC41A3 in Mg2+ homeostasis using the Slc41a3 knockout (Slc41a3−/−) mouse. By quantitative PCR analysis it was shown that Slc41a3 is the only SLC41 isoform with enriched expression in the DCT. Interestingly, serum and urine electrolyte determinations demonstrated that Slc41a3−/− mice suffer from hypomagnesemia. The intestinal Mg2+ absorption capacity was measured using the stable 25Mg2+ isotope in mice fed a low Mg2+ diet. 25Mg2+ uptake was similar in wildtype (Slc41a3+/+) and Slc41a3−/− mice, although Slc41a3−/− animals exhibited increased intestinal mRNA expression of Mg2+ transporters Trpm6 and Slc41a1. Remarkably, some of the Slc41a3−/− mice developed severe unilateral hydronephrosis. In conclusion, SLC41A3 was established as a new factor for Mg2+ handling.