当前位置： SCI文献检索 > JOURNAL OF MOLECULAR AND CELLULAR CARDIOLOGY期刊下所有文献 > Heat-shock protein 90 modulates cardiac ventricular hypertrophy via activation of MAPK pathway.

Heat-shock protein 90 modulates cardiac ventricular hypertrophy via activation of MAPK pathway.

Abstract：

:The Raf/MAPK/ERK kinase (Mek)/extracellular signal-regulated kinases (Erk) pathway is activated in cardiac hypertrophy after a myocardial infarction. Although heat-shock protein 90 (Hsp90) may regulate the Raf/Mek/Erk signal pathway, the role of Hsp90 in pathophysiological cardiac hypertrophy remains unclear. In this study, we examined the role of Hsp90 in this pathway in cardiac hypertrophy under in vivo and in vitro experimental conditions. Cultured rat cardiomyocytes were treated with the Hsp90 inhibitor 17-(allylamino)-17-dimethoxy-geldanamycin (17-AAG) and proteasome inhibitor MG-132, and then incubated with endothelin-1 (ET) to induce hypertrophy of the cells. The ET-induced increase in the cell size was attenuated by 17-AAG pretreatment. Immunoblot analysis revealed that the c-Raf content of ET-treated cardiomyocytes was decreased in the presence of 17-AAG. An increase in phosphorylation levels of Erk1/2 and GATA4 in ET-treated cardiomyocytes was also attenuated by the 17-AAG pretreatment. Myocardial infarction was produced by ligation of the left ventricular coronary artery in rats, and then 17-AAG was intraperitoneally administered to the animals starting from the 2ndweek after coronary artery ligation (CAL). CAL-induced increases in the heart weight and cross-sectional area were attenuated by 17-AAG treatment. CAL rats showed signs of chronic heart failure with cardiac hypertrophy, whereas cardiac function in CAL rats treated with 17-AAG was not reduced. Treatment of CAL rats with 17-AAG caused a decrease in the c-Raf content and Erk1/2 and GATA4 phosphorylation levels. These findings suggest that Hsp90 is involved in the activation of the Raf/Mek/Erk pathway via stabilization of c-Raf in cardiomyocytes, resulting in the development of cardiac hypertrophy following myocardial infarction.

journal_name

J Mol Cell Cardiol

journal_title

Journal of molecular and cellular cardiology

authors

Tamura S,Marunouchi T,Tanonaka K

doi

10.1016/j.yjmcc.2018.12.010

subject

Has Abstract

pub_date

2019-02-01 00:00:00

pages

134-142

eissn

0022-2828

issn

1095-8584

pii

S0022-2828(18)30932-5

journal_volume

127

pub_type

杂志文章

在线工具

Heat-shock protein 90 modulates cardiac ventricular hypertrophy via activation of MAPK pathway.