Guggulsterone antagonizes farnesoid X receptor induction of bile salt export pump but activates pregnane X receptor to inhibit cholesterol 7α-hydroxylase gene
bile acid synthesis;
nuclear receptor;
cholesterol metabolism;
bile acid transport;
pregnane X receptor;
D O I:
10.1016/S0006-291X(03)00551-5
中图分类号:
Q5 [生物化学];
Q7 [分子生物学];
学科分类号:
071010 ;
081704 ;
摘要:
Bile acids activate a nuclear receptor, farnesoid X receptor (FXR), that induces bile salt export pump (BSEP) but inhibits cholesterol 7alpha-hydroxylase (CYP7A1) gene transcription in the liver. Guggulsterone, a plant sterol that lowers serum cholesterol, has been shown to antagonize FXR activated genes. Transient transfection assay of a human BSEP/luciferase reporter in HepG2 cells transfected with FXR reveals that guggulsterone strongly antagonizes bile acid induction of the BSEP gene. On the other hand, guggulsterone has no effect on FXR inhibition of the CYP7A1 gene, but strongly inhibits the human CYP7A1 gene by activation of pregnane X receptor (PXR). These results suggest that guggulsterone inhibits bile acid secretion from hepatocytes into bile and activates PXR to inhibit bile acid synthesis in the liver. Reduced conversion of cholesterol and bile acid excretion may lead to an increase of hepatic cholesterol and decrease of intestinal cholesterol absorption, and results in lowering serum cholesterol. (C) 2003 Elsevier Science (USA). All rights reserved.
机构:
Southern Med Univ, Dept Physiol, 1838 Guangzhou Ave, Guangzhou 510080, Guangdong, Peoples R ChinaSouthern Med Univ, Dept Physiol, 1838 Guangzhou Ave, Guangzhou 510080, Guangdong, Peoples R China
Wang, Jieqin
Huang, Yaowei
论文数: 0引用数: 0
h-index: 0
机构:
Southern Med Univ, Inst Genet Engn, 1838 Guangzhou Ave, Guangzhou 510080, Guangdong, Peoples R ChinaSouthern Med Univ, Dept Physiol, 1838 Guangzhou Ave, Guangzhou 510080, Guangdong, Peoples R China
Huang, Yaowei
Hou, Xusheng
论文数: 0引用数: 0
h-index: 0
机构:
Southern Med Univ, Dept Physiol, 1838 Guangzhou Ave, Guangzhou 510080, Guangdong, Peoples R ChinaSouthern Med Univ, Dept Physiol, 1838 Guangzhou Ave, Guangzhou 510080, Guangdong, Peoples R China
Hou, Xusheng
Wu, Wenyu
论文数: 0引用数: 0
h-index: 0
机构:
Southern Med Univ, Dept Physiol, 1838 Guangzhou Ave, Guangzhou 510080, Guangdong, Peoples R ChinaSouthern Med Univ, Dept Physiol, 1838 Guangzhou Ave, Guangzhou 510080, Guangdong, Peoples R China
Wu, Wenyu
Nie, Lei
论文数: 0引用数: 0
h-index: 0
机构:
Southern Med Univ, Dept Physiol, 1838 Guangzhou Ave, Guangzhou 510080, Guangdong, Peoples R ChinaSouthern Med Univ, Dept Physiol, 1838 Guangzhou Ave, Guangzhou 510080, Guangdong, Peoples R China
Nie, Lei
Tian, Yinghong
论文数: 0引用数: 0
h-index: 0
机构:
Southern Med Univ, Dept Physiol, 1838 Guangzhou Ave, Guangzhou 510080, Guangdong, Peoples R ChinaSouthern Med Univ, Dept Physiol, 1838 Guangzhou Ave, Guangzhou 510080, Guangdong, Peoples R China
Tian, Yinghong
Lu, Yanmeng
论文数: 0引用数: 0
h-index: 0
机构:
Southern Med Univ, Lab Electron Microscopy, 1838 Guangzhou Ave, Guangzhou 510080, Guangdong, Peoples R ChinaSouthern Med Univ, Dept Physiol, 1838 Guangzhou Ave, Guangzhou 510080, Guangdong, Peoples R China
Lu, Yanmeng
Yin, Yanru
论文数: 0引用数: 0
h-index: 0
机构:
Southern Med Univ, Dept Physiol, 1838 Guangzhou Ave, Guangzhou 510080, Guangdong, Peoples R ChinaSouthern Med Univ, Dept Physiol, 1838 Guangzhou Ave, Guangzhou 510080, Guangdong, Peoples R China
机构:
Univ Tokyo, Inst Mol & Cellular Biosci, Tokyo 1130032, JapanUniv Tokyo, Inst Mol & Cellular Biosci, Tokyo 1130032, Japan
Misawa, Takashi
Hayashi, Hisamitsu
论文数: 0引用数: 0
h-index: 0
机构:
Univ Tokyo, Lab Mol Pharmacokinet, Grad Sch Pharmaceut Sci, Bunkyo Ku, Tokyo 1130033, JapanUniv Tokyo, Inst Mol & Cellular Biosci, Tokyo 1130032, Japan
Hayashi, Hisamitsu
Makishima, Makoto
论文数: 0引用数: 0
h-index: 0
机构:
Nihon Univ, Sch Med, Itabashi Ku, Tokyo 1738610, JapanUniv Tokyo, Inst Mol & Cellular Biosci, Tokyo 1130032, Japan
Makishima, Makoto
Sugiyama, Yuichi
论文数: 0引用数: 0
h-index: 0
机构:
Univ Tokyo, Lab Mol Pharmacokinet, Grad Sch Pharmaceut Sci, Bunkyo Ku, Tokyo 1130033, JapanUniv Tokyo, Inst Mol & Cellular Biosci, Tokyo 1130032, Japan
Sugiyama, Yuichi
Hashimoto, Yuichi
论文数: 0引用数: 0
h-index: 0
机构:
Univ Tokyo, Inst Mol & Cellular Biosci, Tokyo 1130032, JapanUniv Tokyo, Inst Mol & Cellular Biosci, Tokyo 1130032, Japan