Electronic Thesis and Dissertation Repository

Junctophilin-2 Protects Cardiomyocytes against Palmitate-induced Injury

Xiaoyun Ji, The University of Western Ontario

Abstract

Cardiac lipotoxicity may induce cardiomyocyte apoptosis, eventually leading to myocardial dysfunction and heart failure. This study investigated whether and how junctophilin-2 (JPH2) plays a role in palmitate-induced apoptosis in cardiomyocytes. Here, we found palmitate incubation reduced JPH2 protein levels, increased cytosolic Ca2+ and induced apoptosis in cardiomyocytes. JPH2 over-expression prevented the increased cytosolic Ca2+ and apoptosis in palmitate-stimulated cardiomyocytes. JPH2 over-expression also attenuated palmitate-induced CCAAT-enhancer-binding protein homologous protein (CHOP) expression and CHOP deletion alleviated palmitate-induced apoptosis. Furthermore, blocking Ca2+ release from ryanodine receptor-2 (RyR2) prevented palmitate-stimulated CHOP induction and apoptosis. Additionally, JPH2 silencing elevated cytosolic Ca2+, induced CHOP expression and apoptosis in cardiomyocytes; these effects of JPH2 silencing were inhibited by blocking Ca2+ release from RyR2. In summary, we demonstrate that JPH2 attenuates palmitate-induced apoptosis by reducing Ca2+ release from RyR2 and preventing CHOP expression in cardiomyocytes. Thus, targeting JPH2 may represent a new therapeutic strategy to treat cardiac lipotoxicity.