Characterization of conjugated and unconjugated bile acid transport via human organic solute transporter α/β
Characterization of conjugated and unconjugated bile acid transport via human organic solute transporter α/β
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DOI：
10.1016/j.bbamem.2019.03.003
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发表时间：
2019-05-01
影响因子：
3.4
通讯作者：
Mano, Nariyasu
中科院分区：
文献类型：
--
作者：
Suga, Takahiro;Yamaguchi, Hiroaki;Mano, Nariyasu
胆汁酸是由肝细胞中的胆固醇生物合成的，通常位于肝肠循环系统中。该系统由在肝脏和肠道中表达的几种转运蛋白调节。有机溶质转运蛋白（OST）α/β，被认为是某些有机阴离子的双向转运蛋白，有助于胆汁酸的转运;然而，对单个胆汁酸的转运特性还不清楚。在这项研究中，我们研究了5种胆汁酸（胆酸[CA]、鹅去氧胆酸[CDCA]、脱氧胆酸[DCA]、熊去氧胆酸[UDCA]和石胆酸[LCA]）及其甘氨酸和牛磺酸结合物通过OST α/β介导的转运特性。在未结合胆汁酸中，OST α β/MDCKII细胞比模拟细胞更快地摄取CA、CDCA、DCA和LCA，但未观察到UDCA摄取的显著增加。相反，所有甘氨酸和牛磺酸结合的胆汁酸显示出OST α β/MDCKII细胞摄取的显著增加。观察到CDCA、DCA、甘氨鹅去氧胆酸（GCDCA）、甘氨脱氧胆酸（GDCA）、甘氨石胆酸（GLCA）、牛磺鹅去氧胆酸（TCDCA）和牛磺石胆酸（TLCA）的可饱和OST α/β介导转运。OST α/β的CDCA、DCA、GCDCA、GDCA、GLCA、TCDCA和TLCA的表观米氏常数分别为23.0 +/- 4.0、14.9 +/- 1.9、864.2 +/- 80.7、586.4 +/- 43.2、12.8 +/- 0.5、723.7 +/- 4.8和23.9 +/- 0.3 μ M。然而，其他胆汁酸的转运是不饱和的。我们的研究结果表明，OST α/β具有低亲和力，但转运胆汁酸的能力高。
Bile acids are biosynthesized from cholesterol in hepatocytes and usually localize in the enterohepatic circulation system. This system is regulated by several transporters that are expressed in the liver and intestine. Organic solute transporter (OST) alpha/beta, which is known as a bidirectional transporter for some organic anions, contributes to the transport of bile acids; however, the transport properties of individual bile acids are not well understood. In this study, we investigated the transport properties of five bile acids (cholic acid [CA], chenodeoxycholic acid [CDCA], deoxycholic acid [DCA], ursodeoxycholic acid [UDCA], and lithocholic acid [LCA]) together with their glycine and taurine conjugates mediated by OST alpha/beta. Of the unconjugated bile acids, CA, CDCA, DCA, and LCA were taken up by OST alpha beta/MDCKII cells more rapidly than mock cells, but no significant increase in the uptake of UDCA was observed. On the contrary, all glycine- and taurine-conjugated bile acids showed a significant increase in the uptake by OST alpha beta/MDCKII cells. Saturable OST alpha/beta-mediated transports of CDCA, DCA, glycochenodeoxycholic acid (GCDCA), glycodeoxycholic acid (GDCA), glycolithocholic acid (GLCA), taurochenodeoxycholic acid (TCDCA), and taurolithocholic acid (TLCA) were observed. The apparent Michaelis constants of CDCA, DCA, GCDCA, GDCA, GLCA, TCDCA, and TLCA for OST alpha/beta were 23.0 +/- 4.0, 14.9 +/- 1.9, 864.2 +/- 80.7, 586.4 +/- 43.2, 12.8 +/- 0.5, 723.7 +/- 4.8, and 23.9 +/- 0.3 mu M, respectively. However, the transport of other bile acids was not saturable. Our results indicate that OST alpha/beta has a low affinity but a high capacity for transporting bile acids.