Regulation of Bilirubin Metabolism by the Receptor CAR

描述（由申请人提供）：核激素受体CAR（组成型雄烷受体）是多种异生物质化合物代谢的关键调节剂。该提议集中于CAR在胆红素代谢途径中的新鉴定的作用。初步结果表明，CAR是小鼠胆红素清除途径的关键调节剂。本项目的总体目标是将这一发现扩展到人类CAR，并开始探索其在新生儿黄疸中的作用以及其在介导一种知名中药治疗黄疸中的作用。本提案的具体目的是：1）确定人CAR在胆红素代谢调节中的作用。2)比较CAR在人新生儿肝脏和成人肝脏中的表达水平。3)确定CAR在介导中药茵栀黄治疗人类黄疸的作用中的作用。这些发现将阐明CAR在胆红素代谢中的重要作用，并对开发治疗人类黄疸和其他相关疾病的更有效药物具有重要意义。

DESCRIPTION (provided by applicant): The nuclear hormone receptor CAR (Constitutive Androstane Receptor) is a key regulator of the metabolism of a wide range of xenobiotic compounds. This proposal is focused on a newly identified role of CAR in the bilirubin metabolism pathway. Preliminary results demonstrate that CAR is a key regulator of bilirubin clearance pathway in mice. The overall goals of this project are to extend this finding to human CAR and begin to explore its role in neonatal jaundice as well as its role in mediating a well-known Chinese medicine in the treatment of jaundice. The specific aims of this proposal are: 1) Determine the role of human CAR in regulation of bilirubin metabolism. 2) Compare the level of expression of CAR in human neonatal livers with adult livers. 3) Determine the role of CAR in mediating the effect of a Chinese medicine, Yinzhi Huang, in treatment of human jaundice. The findings will elucidate the essential role of CAR in bilirubin metabolism and have significant implications for development of more potent drugs for the treatment of human jaundice and other related diseases.