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

Authors: Kee, HJ  Eom, GH  Joung, H  Shin, S  Kim, JR  Cho, YK  Choe, N  Sim, BW  Jo, D  Jeong, MH  Kim, KK  Seo, JS  Kook, H 
Citation: Kee HJ, etal., Circ Res. 2008 Nov 21;103(11):1259-69. Epub 2008 Oct 10.
Pubmed: (View Article at PubMed) PMID:18849323
DOI: Full-text: DOI:10.1161/01.RES.0000338570.27156.84

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.


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CRRD Object Information
CRRD ID: 2306446
Created: 2009-04-16
Species: All species
Last Modified: 2009-04-16
Status: ACTIVE


RGD is funded by grant HL64541 from the National Heart, Lung, and Blood Institute on behalf of the NIH.