Urate transport via human PAH transporter hOAT1 and its gene structure
Urate transport via human PAH transporter hOAT1 and its gene structure
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DOI：
10.1046/j.1523-1755.2003.00710.x
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发表时间：
2003-01-01
影响因子：
19.6
通讯作者：
Endou, H
中科院分区：
文献类型：
--
作者：
Ichida, K;Hosoyamada, M;Endou, H
背景我们最近克隆了人有机阴离子转运蛋白1（hOAT 1）作为对氨基马尿酸（PAH）转运蛋白.尿酸盐是否由PAH转运蛋白在人体内转运仍不清楚。家族性幼年型痛风性肾病（FJGN）被认为是尿酸转运蛋白异常的结果。为了确定hOAT 1是否转运尿酸盐，使用表达hOAT 1的小鼠S2细胞系测定PAH和尿酸盐的细胞摄取，以及无机阴离子、促尿酸和抗促尿酸药物的抑制特征。使用全长hOAT 1 -1 cDNA作为探针，从基因组文库中克隆hOAT 1基因。对两个FJGN姐妹篇的hOAT 1基因编码区进行测序。同时对FJGN患者妹妹的肾脏进行hOAT 1的免疫组织化学荧光分析。尿酸盐通过hOAT 1转运的Km和Vmax值分别为943 +/- 84 mumol/L和1286 +/- 162 pmol/mg蛋白/min。尿酸盐经hOAT 1转运的IC 50顺序为苯溴马隆<丙磺舒<水杨酸或吡嗪羧酸。hOAT 1基因全长10.9kb，有9个内含子。两个患有FJGN的姐妹篇的hOAT 1基因编码区的突变检测不到。免疫组化荧光染色显示，妹妹肾脏中hOAT 1的表达与对照组相似。我们的数据表明，hOAT 1转运尿酸盐，并定义了促尿酸和抗促尿酸药物的抑制特征。hOAT 1在本研究中检查的两姐妹篇中不负责FJGN。
Background. We recently cloned the human organic anion transporter 1 (hOAT1) as a p -aminohippurate (PAH) transporter. Whether urate is transported by the PAH transporter in humans remains unclear. Familial juvenile gouty nephropathy (FJGN) is thought to develop as a result of an abnormality in the urate transporter.Methods. To determine if hOAT1 transported urate, the cellular uptakes of PAH and urate were determined, as were the inhibition profiles of inorganic anions, and uricosuric and antiuricosuric agents using a mouse S2 cell line expressing hOAT1. The hOAT1 gene was cloned from a genomic library using full-length hOAT1-1 cDNA as a probe. The coding regions of the hOAT1 genes of two sisters with FJGN were sequenced. Also, immunohistochemical fluorescence analysis of hOAT1 in the kidney of the younger sister with FJGN was performed.Results. The K-m and V-max values of urate transport via hOAT1 were 943 +/- 84 mumol/L and 1286 +/- 162 pmol/mg protein/min, respectively. The order of the IC50 of urate transport via hOAT1 was benzbromarone < probenecid < salicylate or pyrazine carboxylic acid. The 10.9 kb hOAT1 gene was found to be interrupted by nine introns. Mutations in the coding region of the hOAT1 gene from the two sisters with FJGN were undetectable. Immunohistochemical fluorescent staining showed that hOAT1 in the kidney of the younger sister was similar to that of control individuals.Conclusions. Our data show that hOAT1 transports urate, and the inhibition profiles of uricosuric and antiuricosuric agents are defined. hOAT1 is not responsible for FJGN in the two sisters examined in this study.