Renal Solute Transporters and Their Relevance to Serum Urate Disorder
Renal Solute Transporters and Their Relevance to Serum Urate Disorder
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DOI：
10.2174/157340210791936732
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发表时间：
2010-01-01
影响因子：
2.3
通讯作者：
Endou, Hitoshi
中科院分区：
文献类型：
--
作者：
Anzai, Naohiko;Jutabha, Promsuk;Endou, Hitoshi
由于尿酸(尿酸)是嘌呤代谢的最终产物，具有抗氧化活性，因此它对氧化应激的保护作用变得引人注目。血清尿酸水平低与多发性硬化症、帕金森氏症和阿尔茨海默病有关。尽管有有益的作用，但高尿酸血症与痛风、高血压、心血管疾病(如心肌梗死和中风)以及肾脏疾病(如急性尿酸盐肾病和肾结石)有关。肾脏的尿酸转运系统是血尿酸水平的重要决定因素，但其分子机制尚不清楚。2002年，我们的小组发现了URAT1(SLC22A12)，它是一种肾尖尿酸/阴离子交换器，导致了有关参与尿酸盐在肾脏中转运的单个分子的信息积累。2008年，我们对易化葡萄糖转运蛋白家族成员GLUT9(SLC2A9)进行了功能研究，发现其为电压驱动的尿酸转运蛋白URATv1。对一例SLC2A9基因缺陷的肾性低尿酸血症患者的分析表明，尿酸重吸收途径的主要途径是在肾近端小管的基底外侧，尿酸通过顶端URAT1进入尿腔，细胞内的尿酸通过基底外侧URATv1从细胞内排出到间质/血液空间。在这篇综述中，介绍了关于这些分子的最新发现。
Since uric acid (urate), the final product of purine metabolism, exhibits antioxidative activity, its protective role against oxidative stress becomes attractive. Low serum urate levels have been associated with multiple sclerosis, Parkinson's disease, and Alzheimer's disease. Despite its beneficial role, hyperuricemia is associated with gout, hyper-tension, cardiovascular diseases such as myocardial infarction and stroke, and renal diseases such as acute urate nephro-pathy and nephrolithiasis. The urate transport system of the kidney is an important determinant of the serum urate level, but clarification of its molecular mechanism remains incomplete. In 2002, our group identified URAT1 (SLC22A12), a renal apical urate/anion exchanger, leading to the accumulation of information concerning individual molecules involved in urate transport in the kidney. In 2008, we functionally characterized facilitatory glucose transporter family member GLUT9 (SLC2A9) as a voltage-driven urate transporter URATv1 and analysis of a renal hypouricemia patient with a genetic defect in SLC2A9 have established the main route of the urate reabsorption pathway at the basolateral side of renal proximal tubules, where urate in the urinary lumen is taken up via apical URAT1 and intracellular urate exits from the cell to the interstitium/blood space via basolateral URATv1. In this review, recent findings concerning these molecules are presented.