Downregulation of organic anion transporters in rat kidney under ischemia/reperfusion-induced qacute renal failure
Downregulation of organic anion transporters in rat kidney under ischemia/reperfusion-induced qacute renal failure
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DOI：
10.1038/sj.ki.5002104
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发表时间：
2007-03-01
影响因子：
19.6
通讯作者：
Saito, H.
中科院分区：
文献类型：
--
作者：
Matsuzaki, T.;Watanabe, H.;Saito, H.
检测大鼠肾脏缺血/再灌注（I/R）引起的急性肾衰竭（ARF）对有机阴离子转运蛋白（OAT）表达的影响。血清硫酸吲哚酚 (IS) 是一种尿毒症毒素，也是肾小管中 OAT 的底物，其水平随着 ARF 的进展而显着增加。然而，摄入钴后这种增加会显着减弱。缺血肾脏中rOAT1和rOAT3的mRNA和蛋白水平均显着降低。与对照大鼠相比，缺血大鼠肾切片对对氨基马尿酸（PAH）和硫酸雌酮（ES）的摄取显着减少。取自用钴处理的缺血大鼠的肾切片显示 ES 摄取水平显着升高。钴摄入量不影响 PAH 摄取，表明 rOAT3 功能恢复，但 rOAT1 没有恢复。缺血肾中 Na+/K+-ATPase 的表达显着降低，表明肾小管细胞中向内的 Na+ 梯度已崩溃，从而降低了 α-酮戊二酸的向外梯度，α-酮戊二酸是两种 rOAT 的驱动力。钴处理显着恢复了 Na+/K+-ATPase 表达的降低。我们的结果表明，肾rOAT1和rOAT3的下调可能是缺血大鼠血清IS水平升高的原因。钴治疗对缺血引起的 ARF 有显着的保护作用，并伴有 rOAT3 和/或 Na+/K+-ATPase 功能的恢复。
The effect of acute renal failure (ARF) induced by ischemia/ reperfusion (I/R) of rat kidney on the expression of organic anion transporters (OATs) was examined. The level of serum indoxyl sulfate ( IS), a uremic toxin and substrate of OATs in renal tubules, shows a marked increase with the progression of ARF. However, this increase was significantly attenuated by ingestion of cobalt. The level of mRNA and protein of both rOAT1 and rOAT3 were markedly depressed in the ischemic kidney. The uptake of p-aminohippuric acid (PAH) and estrone sulfate (ES) by renal slices of ischemic rats was significantly reduced compared to control rats. Renal slices taken from ischemic rats treated with cobalt displayed significantly elevated levels of ES uptake. Cobalt intake did not affect PAH uptake, indicating the functional restoration of rOAT3 but not rOAT1. The expression of Na+/K+-ATPase was markedly depressed in the ischemic kidney, suggesting that the inward Na+ gradient in renal tubular cells had collapsed, thereby reducing the outward gradient of alpha-ketoglutarate, a driving force of both rOATs. The decreased expression of Na+/K+-ATPase was significantly restored by cobalt treatment. Our results suggest that the downregulation of renal rOAT1 and rOAT3 could be responsible for the increase in serum IS level of ischemic rats. Cobalt treatment has a significant protective effect on ischemia-induced ARF, being accompanied by the restoration of rOAT3 and/or Na+/K+-ATPase function.