Troglitazone is an estrogen-related receptor a and γ inverse agonist

被引：15

作者：

Wang, Yanfei ^{[1
]}

Fang, Fang ^{[1
]}

Wong, Chi-Wai ^{[1
]}

机构：

[1] Chinese Acad Sci, Guangzhou Inst Biomed & Hlth, Guangzhou 510663, Guangdong, Peoples R China

来源：

BIOCHEMICAL PHARMACOLOGY | 2010年 / 80卷 / 01期

关键词：

Troglitazone; ERR alpha; ERR gamma; Mitochondrial biogenesis; ROS; COACTIVATOR; ALPHA; EXPRESSION; GROWTH; CANCER; LUNG; THIAZOLIDINEDIONES; INHIBITION; GLITAZONES; PROSTATE;

D O I：

10.1016/j.bcp.2010.03.013

中图分类号：

R9 [药学];

学科分类号：

100702 [药剂学];

摘要：

As a ligand for peroxisome proliferators-activated receptor gamma (PPAR gamma), troglitazone inhibits cell growth by mechanisms besides activating PPAR gamma. In this study, we found that troglitazone interfered with the interactions between estrogen-related receptor alpha and gamma (ERR alpha and ERR gamma) and their coactivator PPAR gamma coactivator-1 alpha (PCC-1 alpha) functioning as an inverse agonist. Additionally, troglitazone suppressed the expressions of PGC-1 alpha and its related member PGC-1 beta which are key regulators of mitochondrial function. Consequently, troglitazone reduced mitochondrial mass and suppressed the expressions of superoxide dismutases to elevate reactive oxygen species (ROS) production. The increase in ROS in turn induced the expression of cell cycle inhibitor p21(WAF1). we therefore propose that ERR alpha and ERR gamma are alternative targets of troglitazone important for mediating its growth suppressive effect. (C) 2010 Elsevier Inc. All rights reserved.

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页码：80 / 85

页数：6

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