Activation of peroxisome proliferator-activated receptor gamma inhibits endothelin-1-induced cardiac hypertrophy via the calcineurin/NFAT signaling pathway

被引：54

作者：

Bao, Yingxia ^{[1
]}

Li, Ruifang ^{[1
]}

Jiang, Jianmin ^{[1
]}

Cai, Birong ^{[1
]}

Gao, Jie ^{[1
]}

Le, Kang ^{[1
]}

Zhang, Fangyan ^{[1
]}

Chen, Shaorui ^{[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：

MOLECULAR AND CELLULAR BIOCHEMISTRY | 2008年 / 317卷 / 1-2期

基金：

中国国家自然科学基金;

关键词：

peroxisome proliferator-activated receptor gamma; calcineurin; nuclear factor of activated T-cell; endothelin-1; cardiac hypertrophy;

D O I：

10.1007/s11010-008-9848-8

中图分类号：

Q2 [细胞生物学];

学科分类号：

071009 [细胞生物学]; 090102 [作物遗传育种];

摘要：

Peroxisome proliferator-activated receptor gamma (PPAR-gamma) has been described as a negative regulator of cardiac hypertrophy. A better understanding of PPAR-gamma and cardiac hypertrophy may facilitate the development of novel therapeutic strategies to treat heart diseases related to cardiac hypertrophy by mimicking the naturally preferred mechanisms. In the present study, we investigated the interaction between PPAR-gamma and calcineurin/nuclear factor of activated T-cells (NFAT) in endothelin-1 (ET-1)-induced hypertrophy of neonatal rat cardiac myocytes. The results suggest that the treatment of cultured cardiac myocytes with a PPAR-gamma ligand, rosiglitazone, inhibited the ET-1-induced increase in protein synthesis, surface area, calcineurin enzymatic activity, and protein expression. Both the application of rosiglitazone and overexpression of the PPAR-gamma inhibited the nuclear translocation of NFATc4. Moreover, co-immunoprecipitation studies showed that rosiglitazone enhanced the association between PPAR-gamma and calcineurin/NFAT. These results suggest that ET-1-induced cardiac hypertrophy is inhibited by activation of PPAR-gamma, which is at least partly due to cross-talk between PPAR-gamma and calcineurin/NFAT.

引用

页码：189 / 196

页数：8

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