Identification of a novel gene family encoding human liver-specific organic anion transporter LST-1

被引:442
作者
Abe, T
Kakyo, M
Tokui, T
Nakagomi, R
Nishio, T
Nakai, D
Nomura, H
Unno, M
Suzuki, M
Naitoh, T
Matsuno, S
Yawo, H
机构
[1] Tohoku Univ, Sch Med, Dept Neurophysiol, Aoba Ku, Sendai, Miyagi 9808575, Japan
[2] Tohoku Univ, Sch Med, Dept Surg 1, Aoba Ku, Sendai, Miyagi 9808575, Japan
[3] Tohoku Univ, Sch Med, Dept Pediat, Aoba Ku, Sendai, Miyagi 9808575, Japan
[4] Sankyo Co Ltd, Analyt & Metab Res Labs, Tokyo 1408710, Japan
关键词
D O I
10.1074/jbc.274.24.17159
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
We have isolated a novel liver-specific organic anion transporter, LST-1, that is expressed exclusively in the human, rat, and mouse liver. LST-1 is a new gene family located between the organic anion transporter family and prostaglandin transporter. LST-1 transports taurocholate (K-m = 13.6 mu M) in a sodium-independent manner. LST-1 also shows broad substrate specificity. It transports conjugated steroids (dehydroepiandrosterone sulfate, estradiol-17 beta-glucuronide, and estrone-3-sulfate), eicosanoids (prostaglandin E-2, thromboxane B-2, leukotriene C-4, leukotriene E-4), and thyroid hormones (thyroxine, K-m = 3.0 mu M and triiodothyronine, K-m = 2.7 mu M), reflecting hepatic multispecificity. LST-1 is probably the most important transporter in human Liver for clearance of bile acids and organic anions because hepatic levels of another organic anion transporter, OATP, is very low. This is also the first report of the human molecule that transports thyroid hormones.
引用
收藏
页码:17159 / 17163
页数:5
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