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Carboxyl terminus of Hsp70‐interacting protein (CHIP) is required to modulate cardiac hypertrophy and attenuate autophagy during exercise
Author(s) -
Willis Monte S.,
Min JinNa,
Wang Shaobin,
McDonough Holly,
Lockyer Pamela,
Wadosky Kristine M.,
Patterson Cam
Publication year - 2013
Publication title -
cell biochemistry and function
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.933
H-Index - 61
eISSN - 1099-0844
pISSN - 0263-6484
DOI - 10.1002/cbf.2962
Subject(s) - autophagy , cardioprotection , muscle hypertrophy , hsp70 , ubiquitin , cardiac function curve , protein kinase b , ubiquitin ligase , cardiac hypertrophy , medicine , ischemia , microbiology and biotechnology , biology , heat shock protein , heart failure , apoptosis , signal transduction , biochemistry , gene
The carboxyl terminus of Hsp70‐interacting protein (CHIP) is a ubiquitin ligase/cochaperone critical for the maintenance of cardiac function. Mice lacking CHIP (CHIP−/−) suffer decreased survival, enhanced myocardial injury and increased arrhythmias compared with wild‐type controls following challenge with cardiac ischaemia reperfusion injury. Recent evidence implicates a role for CHIP in chaperone‐assisted selective autophagy, a process that is associated with exercise‐induced cardioprotection. To determine whether CHIP is involved in cardiac autophagy, we challenged CHIP−/− mice with voluntary exercise. CHIP−/− mice respond to exercise with an enhanced autophagic response that is associated with an exaggerated cardiac hypertrophy phenotype. No impairment of function was identified in the CHIP−/− mice by serial echocardiography over the 5 weeks of running, indicating that the cardiac hypertrophy was physiologic not pathologic in nature. It was further determined that CHIP plays a role in inhibiting Akt signalling and autophagy determined by autophagic flux in cardiomyocytes and in the intact heart. Taken together, cardiac CHIP appears to play a role in regulating autophagy during the development of cardiac hypertrophy, possibly by its role in supporting Akt signalling, induced by voluntary running in vivo . Copyright © 2013 John Wiley & Sons, Ltd.