期刊
BIOCHEMICAL PHARMACOLOGY
卷 80, 期 1, 页码 80-85出版社
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.bcp.2010.03.013
关键词
Troglitazone; ERR alpha; ERR gamma; Mitochondrial biogenesis; ROS
资金
- National Basic Research Program of China [2006CB50390]
- Chinese Academy of Sciences [KSCX2-YW-R-085]
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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