Activation of peroxisome proliferator-activated receptor-α prevents glycogen synthase 3β phosphorylation and inhibits cardiac hypertrophy

被引：47

作者：

Li, Ruifang ^{[1
]}

Zheng, Wenhua ^{[1
]}

Pi, Rongbiao ^{[1
]}

Gao, Jie ^{[1
]}

Zhang, Huijie ^{[1
]}

Le, Ping Wang Kang ^{[1
]}

Liu, Peiqing ^{[1
]}

机构：

[1] Sun Yat Sen Univ, Sch Pharmaceut Sci, Lab Pharmacol & Toxicol, Guangzhou 510080, Guangdong, Peoples R China

来源：

FEBS LETTERS | 2007年 / 581卷 / 17期

基金：

中国国家自然科学基金;

关键词：

peroxisome proliferator-activated receptor-alpha; cardiac hypertrophy; glycogen synthase kinase; nuclear factor of activated T cells;

D O I：

10.1016/j.febslet.2007.06.017

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：

Activation of peroxisome proliferator-activated receptor-alpha (PPAR-alpha) has been recently reported to inhibit vascular inflammatory response and prevent cardiac hypertrophy. However, it is unclear how the activation of PPAR-a regulates hypertrophic response. In the present study, we found that application of fenofibrate and overexpression of PPAR-a inhibited endothelin-1 (ET-1)-induced phosphorylation of protein kinase B (Akt) at Ser473 and glycogen synthase kinase3 beta (GSK3 beta) at Ser9, and prevented ET-1-induced nuclear translocation of NFATc4 in cardiomyocytes. Moreover, co-immunoprecipitation studies showed that fenofibrate strongly induced the association of nuclear factor of activated T cells (NFATc4) with PPAR-a. These results suggest that activation of PPAR-a inhibits ET-1-induced cardiac hypertrophy through regulating PI3K/Akt/GSK3R and NFAT signaling pathways. (C) 2007 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.

引用

页码：3311 / 3316

页数：6

共 27 条

[1] Deactivation of peroxisome proliferator-activated receptor-α during cardiac hypertrophic growth [J].