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核受体对胆汁酸和外源性化学物质的代谢：一种协调解毒系统，对健康和疾病有影响。

Nuclear Receptor Metabolism of Bile Acids and Xenobiotics: A Coordinated Detoxification System with Impact on Health and Diseases.

机构信息

Université Clermont Auvergne, GReD, CNRS UMR6293, INSERM U1103, 28, Place Henri Dunant, BP38, F63001 Clermont-Ferrand, France.

Centre de Recherche en Nutrition Humaine d'Auvergne, 58 Boulevard Montalembert, F-63009 Clermont-Ferrand, France.

出版信息

Int J Mol Sci. 2018 Nov 17;19(11):3630. doi: 10.3390/ijms19113630.

DOI:10.3390/ijms19113630
PMID:30453651
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC6274770/
Abstract

Structural and functional studies have provided numerous insights over the past years on how members of the nuclear hormone receptor superfamily tightly regulate the expression of drug-metabolizing enzymes and transporters. Besides the role of the farnesoid X receptor (FXR) in the transcriptional control of bile acid transport and metabolism, this review provides an overview on how this metabolic sensor prevents the accumulation of toxic byproducts derived from endogenous metabolites, as well as of exogenous chemicals, in coordination with the pregnane X receptor (PXR) and the constitutive androstane receptor (CAR). Decrypting this network should provide cues to better understand how these metabolic nuclear receptors participate in physiologic and pathologic processes with potential validation as therapeutic targets in human disabilities and cancers.

摘要

在过去的几年中，结构和功能研究提供了许多关于核激素受体超家族成员如何紧密调节药物代谢酶和转运体表达的见解。除了法尼醇 X 受体 (FXR) 在胆汁酸转运和代谢的转录控制中的作用外，本综述还概述了这种代谢传感器如何与孕烷 X 受体 (PXR) 和组成型雄烷受体 (CAR) 协调，防止内源性代谢物和外源性化学物质的有毒副产物的积累。 解析这个网络应该为更好地理解这些代谢核受体如何参与生理和病理过程提供线索，并有可能成为人类残疾和癌症的治疗靶点。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ac7c/6274770/dd66f1c71d12/ijms-19-03630-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ac7c/6274770/dde4d9d1fb76/ijms-19-03630-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ac7c/6274770/13dbccc6c528/ijms-19-03630-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ac7c/6274770/dd66f1c71d12/ijms-19-03630-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ac7c/6274770/dde4d9d1fb76/ijms-19-03630-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ac7c/6274770/13dbccc6c528/ijms-19-03630-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ac7c/6274770/dd66f1c71d12/ijms-19-03630-g003.jpg

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Structural insights into the heterodimeric complex of the nuclear receptors FXR and RXR.
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