Carboxyl terminus of Hsp70-interacting protein (CHIP) is required to modulate cardiac hypertrophy and attenuate autophagy during exercise

Monte S. Willis, Jin Na Min, Shaobin Wang, Holly Mcdonough, Pamela Lockyer, Kristine M. Wadosky, Cam Patterson

Research output: Contribution to journalArticle

27 Scopus citations

Abstract

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 5weeks 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.

Original languageEnglish (US)
Pages (from-to)724-735
Number of pages12
JournalCell Biochemistry and Function
Volume31
Issue number8
DOIs
StatePublished - Dec 2013
Externally publishedYes

Keywords

  • Autophagy
  • CHIP
  • Cardiac hypertrophy
  • Heart
  • IGF-1 signalling
  • Ubiquitin ligase

ASJC Scopus subject areas

  • Biochemistry
  • Clinical Biochemistry
  • Cell Biology

Fingerprint Dive into the research topics of 'Carboxyl terminus of Hsp70-interacting protein (CHIP) is required to modulate cardiac hypertrophy and attenuate autophagy during exercise'. Together they form a unique fingerprint.

  • Cite this