胆汁酸：一种孤儿核受体的天然配体。

Bile acids: natural ligands for an orphan nuclear receptor.

作者信息

Parks D J, Blanchard S G, Bledsoe R K, Chandra G, Consler T G, Kliewer S A, Stimmel J B, Willson T M, Zavacki A M, Moore D D, Lehmann J M

机构信息

Department of Molecular Biochemistry, Glaxo Wellcome Research and Development, Research Triangle Park NC, 27709, USA.

出版信息

Science. 1999 May 21;284(5418):1365-8. doi: 10.1126/science.284.5418.1365.

DOI:10.1126/science.284.5418.1365

PMID:10334993

Abstract

Bile acids regulate the transcription of genes that control cholesterol homeostasis through molecular mechanisms that are poorly understood. Physiological concentrations of free and conjugated chenodeoxycholic acid, lithocholic acid, and deoxycholic acid activated the farnesoid X receptor (FXR; NR1H4), an orphan nuclear receptor. As ligands, these bile acids and their conjugates modulated interaction of FXR with a peptide derived from steroid receptor coactivator 1. These results provide evidence for a nuclear bile acid signaling pathway that may regulate cholesterol homeostasis.

摘要

胆汁酸通过人们知之甚少的分子机制调节控制胆固醇稳态的基因转录。游离型和结合型鹅去氧胆酸、石胆酸及脱氧胆酸的生理浓度可激活法尼醇X受体（FXR；NR1H4），一种孤儿核受体。作为配体，这些胆汁酸及其共轭物可调节FXR与类固醇受体辅激活因子1衍生肽的相互作用。这些结果为可能调节胆固醇稳态的核胆汁酸信号通路提供了证据。