Activation of histone deacetylase 2 by inducible heat shock protein 70 in cardiac hypertrophy.

Content Provider	Semantic Scholar
Author	Kee, Hae Jin Eom, Gwang Hyeon Joung, Hosouk Shin, Sera Kim, Ju-Ryoung Cho, Young Kuk Choe, Nakwon Sim, Bo-Woong Jo, Daewoong Jeong, Myung Ho Kim, Kyung Keun Seo, Jeong-Sun Kook, Hyun Seok
Copyright Year	2008
Abstract	Diverse cardiac diseases induce cardiac hypertrophy, which leads to dilatation and heart failure. We previously reported that hypertrophy can be blocked by class I histone deacetylase (HDAC) inhibitor, which prompted us to investigate the regulatory mechanism of class I HDACs. Cardiac hypertrophy was introduced by aortic banding, by infusion of isoproterenol or angiotensin II, or by swimming. Hypertrophic stimuli transiently elevated the activity of histone deacetylase-2 (Hdac2), a class I HDAC. In cardiomyocytes, forced expression of Hdac2 simulated hypertrophy in an Akt-dependent manner, whereas enzymatically inert Hdac2 H141A failed to do so. Hypertrophic stimuli induced the expression of heat shock protein (Hsp)70. The induced Hsp70 physically associated with and activated Hdac2. Hsp70 overexpression produced a hypertrophic phenotype, which was blocked either by siHdac2 or by a dominant negative Hsp70DeltaABD. In Hsp70.1(-/-) mice, cardiac hypertrophy and Hdac2 activation were significantly blunted. Heat shock either to cardiomyocytes or to mice activated Hdac2 and induced hypertrophy. However, heat shock-induced Hdac2 activation was blunted in the cardiomyocytes isolated from Hsp70.1(-/-) mice. These results suggest that the induction of Hsp70 in response to diverse hypertrophic stresses and the ensuing activation of HDAC2 trigger cardiac hypertrophy, emphasizing HSP70/HDAC2 as a novel mechanism regulating hypertrophy.
Starting Page	108
Ending Page	114
Page Count	7
File Format	PDF HTM / HTML
Alternate Webpage(s)	http://circres.ahajournals.org/content/circresaha/103/11/1259.full.pdf?download=true
PubMed reference number	18849323v1
Alternate Webpage(s)	https://doi.org/10.1161/01.RES.0000338570.27156.84
DOI	10.1161/01.res.0000338570.27156.84
Journal	Circulation research
Volume Number	103
Issue Number	11
Language	English
Access Restriction	Open
Subject Keyword	Angiotensin II Angiotensins Cardiac Hypertrophy Dilate procedure Dominant-Negative Mutation HDAC2 gene HSP72 Heat-Shock Proteins Heart Diseases Heart failure Heat shock proteins Heat-Shock Proteins 70 Heat-Shock Response Histones Hypertrophic disorder of skin, unspecified Isoproterenol Myocytes, Cardiac Proto-Oncogene Proteins c-akt histone deacetylase 2
Content Type	Text
Resource Type	Article