Role of CAR and PXR in xenobiotic sensing and metabolism.
Role of CAR and PXR in xenobiotic sensing and metabolism.
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DOI：
10.1517/17425255.2012.685237
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发表时间：
2012-07
影响因子：
4.3
通讯作者：
Chen T
中科院分区：
文献类型：
--
作者：
Wang YM;Ong SS;Chai SC;Chen T
异种生物解毒系统由药物代谢酶和转运体组成，它们的表达受孕烷X受体(PXR)和构成雄烷受体(CAR)的调节，保护人体免受外来化学物质的伤害。最近的大量研究取得的进展要求及时进行审查，以总结和突出这些重要发现。本文综述了近年来在阐明PXR和CAR在异种生物解毒系统中的作用方面的最新进展，重点介绍了在翻译后水平上对PXR和CAR活性调节的理解进展，以及这两种异生感受器调节的结构基础。未来需要努力发现具有物种和异构体选择性的新型激动剂和拮抗剂，在多个水平(转录、转录后和翻译后水平)系统地了解PXR和CAR对外源生物暴露的调节，并解决全长受体的结构，这将通过改进的蛋白质表达和纯化技术和方法来实现。此外，还需要更多的努力来验证PXR和CAR作为疾病相关治疗靶点的有效性，从而扩大它们作为主要异源传感器的作用。
The xenobiotic detoxification system, which protects the human body from external chemicals, comprises drug-metabolizing enzymes and transporters whose expressions are regulated by pregnane X receptor (PXR) and the constitutive androstane receptor (CAR). The progress made in a large number of recent studies calls for a timely review to summarize and highlight these key discoveries. This review summarizes recent advances in elucidating the roles of PXR and CAR in the xenobiotic detoxification system and highlights the progress in understanding the regulation of PXR and CAR activity at the post-translational levels, as well as the structural basis for the regulation of these two xenobiotic sensors. Future efforts are needed to discover novel agonists and antagonists with species and isoform selectivity, to systematically understand the regulation of PXR and CAR at multiple levels (transcriptional, post-transcriptional, and post-translational levels) in response to xenobiotics exposure, and to solve the structures of the full-length receptors, which will be enabled by improved protein expression and purification techniques and approaches. In addition, more efforts will be needed to validate PXR and CAR as disease-related therapeutic targets and thus expand their roles as master xenobiotic sensors.
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