The role of Tel2 in mTOR-mediated cardiac function

Abstract

Previously we showed that the expression of the mechanistic target of rapamycin (mTOR) increases in heart failure, and the cardiac mTOR is sufficient to protect the heart against ischemic stresses. Recent studies demonstrated that telomere maintenance 2 (Tel2) stabilizes mTOR in other tissues. In this study, we examined whether Tel2 is sufficient to stabilize cardiac mTOR and prevent cell death against hypoxia. Overexpression of Tel2 in cardiomyocytes (CMs) increases mTOR and activates both mTORC1 and mTORC2. Overexpression of Tel2 protects CM against hypoxia. Gene silencing by siRNA targeting Tel2 showed that Tel2 is necessary for stabilizing mTOR in cardiomyocytes. We assessed cell shortening and Ca2+ transients as indicators of cardiac function. Preliminary studies of Tel2-overexpressed mTOR-Tg suggest that Tel2 positively regulates contraction and Ca2+ transients via stabilization of mTOR. A study of Tel2-mediated mTOR activation would provide a novel therapeutic target for a therapy of heart failure.