Bile acids: Natural ligands for an orphan nuclear receptor

被引：1880

作者：

Parks, DJ

Blanchard, SG

Bledsoe, RK

Chandra, G

Consler, TG

Kliewer, SA

Stimmel, JB

Willson, TM ^{[1
]}

Zavacki, AM

Moore, DD

Lehmann, JM

机构：

[1] Glaxo Wellcome Inc, Res & Dev, Dept Med Chem, Res Triangle Pk, NC 27709 USA

[2] Glaxo Wellcome Inc, Res & Dev, Dept Mol Sci, Res Triangle Pk, NC 27709 USA

[3] Glaxo Wellcome Inc, Res & Dev, Dept Mol Biochem, Res Triangle Pk, NC 27709 USA

[4] Baylor Coll Med, Dept Cell Biol, Houston, TX 77030 USA

来源：

SCIENCE | 1999年 / 284卷 / 5418期

关键词：

D O I：

10.1126/science.284.5418.1365

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

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.

引用

页码：1365 / 1368

页数：4