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首页> 外文期刊>Cellular Physiology and Biochemistry >Identification of a novel organic anion transporter mediating carnitine transport in mouse liver and kidney
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Identification of a novel organic anion transporter mediating carnitine transport in mouse liver and kidney

机译：介导肉碱在小鼠肝脏和肾脏中运输的新型有机阴离子转运蛋白的鉴定

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摘要

This study identifies a novel organic anion transporter Oat9 expressed in mouse liver and kidney. Two variants were detected by screening a mouse liver cDNA library; these varients consist of 1815 (designated Oat9S) and 2165 (Oat9L) base pairs which encode 443 and 551 amino acid proteins, respectively. Oat9S has a predicted structure containing eight transmembrane domains (TMD); whereas, Oat9L possesses twelve TMD. Oat9 mRNA expression was detected in kidney and liver. This transporter was located at the apical side of the late portion of proximal tubules and at the sinusoidal side of hepatocytes. When expressed in Xenopus oocytes, Oat9S mediated the transport of L-carnitine (Km = 2.9 μM), a representative zwitterion, as well as cimetidine (Km = 16.1 μM) and salicylic acid (Km = 175.5 μM), while Oat9L did not show any transport activity. Oat9S-mediated L-carnitine uptake was inhibited by D-carnitine, acetylcarnitine, octanoylcarnitine, betaine, and other organic compounds, suggesting that quaternary ammonium cation bulkiness and relative hydrophobicity are important factors for Oat9S-substrate interactions. Among OATs, Oat9S appears to be the first member to mediate the transport of carnitine and possesses eight TMD. Overall, these new results provide added insight into the structure-activity relationship comprising the organic ion-permeation pathway. Copyright
机译：这项研究确定了在小鼠肝脏和肾脏中表达的新型有机阴离子转运蛋白Oat9。通过筛选小鼠肝脏cDNA文库检测到两个变体。这些变体由1815个（称为Oat9S）和2165个（Oat9L）碱基对组成，分别编码443和551个氨基酸蛋白质。 Oat9S具有包含八个跨膜结构域（TMD）的预测结构;而Oat9L具有十二个TMD。在肾脏和肝脏中检测到Oat9 mRNA表达。该转运蛋白位于近端肾小管末梢的顶侧和肝细胞的正弦侧。当在非洲爪蟾卵母细胞中表达时，Oat9S介导左旋肉碱（Km = 2.9μM），代表性的两性离子以及西咪替丁（Km = 16.1μM）和水杨酸（Km = 175.5μM）的转运，而Oat9L没有显示出任何运输活动。 Oat9S介导的L-肉碱的摄取受到D-肉碱，乙酰肉碱，辛酰基肉碱，甜菜碱和其他有机化合物的抑制，这表明季铵阳离子的蓬松度和相对疏水性是Oat9S与底物相互作用的重要因素。在OAT中，Oat9S似乎是第一个介导肉碱运输的成员，拥有8种TMD。总体而言，这些新结果为包含有机离子渗透途径的结构-活性关系提供了更多的见识。版权

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