Nuclear-receptor-mediated regulation of drug- and bile-acid-transporter proteins in gut and liver.
Nuclear-receptor-mediated regulation of drug- and bile-acid-transporter proteins in gut and liver.
复制标题
核受体介导的肠道和肝脏蛋白质和胆汁酸转运蛋白的调节。
DOI：
10.3109/03602532.2012.748793
复制
发表时间：
2013-02
影响因子：
5.9
通讯作者：
Cui W
中科院分区：
文献类型：
--
作者：
Staudinger JL;Woody S;Sun M;Cui W
药物不良事件（ADE）是患者发病和死亡的常见原因，通常认为部分原因是药物代谢肝酶的表达和活性变化。目前已知，肠道和肝脏中编码药物和胆汁酸转运蛋白的基因表达的改变在确定患者药物反应和最终临床结果方面发挥了以前未被认识到的作用。四个核受体（NR）超家族成员，包括甾烷X受体（PXR，NR1I2）、组成型雄烷受体（NR1I3）、法尼醇X受体（NR1H4）和维生素D受体（NR1I1），在药物和胆汁酸激活的基因表达程序中起关键作用，以协调调节药物和胆汁酸在肠和肝中的转运活性。本文就NR介导的药物和胆汁酸转运蛋白基因激活及其可能的分子机制作一综述。
Adverse drug events (ADEs) are a common cause of patient morbidity and mortality and are classically thought to result, in part, from variation in expression and activity of hepatic enzymes of drug metabolism. It is now known that alterations in the expression of genes that encode drug- and bile-acid–transporter proteins in both the gut and liver play a previously unrecognized role in determining patient drug response and eventual clinical outcome. Four nuclear receptor (NR) superfamily members, including pregnane X receptor (PXR, NR1I2), constitutive androstane receptor (NR1I3), farnesoid X receptor (NR1H4), and vitamin D receptor (NR1I1), play pivotal roles in drug- and bile-acid– activated programs of gene expression to coordinately regulate drug- and bile-acid transport activity in the intestine and liver. This review focuses on the NR-mediated gene activation of drug and bile-acid transporters in these tissues as well as the possible underlying molecular mechanisms.