Keto acid metabolites of branched-chain amino acids inhibit oxidative stress-induced necrosis and attenuate myocardial ischemia-reperfusion injury.

ABSTRACT: Branched chain α-keto acids (BCKAs) are endogenous metabolites of branched-chain amino acids (BCAAs). BCAA and BCKA are significantly elevated in pathologically stressed heart and contribute to chronic pathological remodeling and dysfunction. However, their direct impact on acute cardiac injury is unknown. Here, we demonstrated that elevated BCKAs significantly attenuated ischemia-reperfusion (I/R) injury and preserved post I/R function in isolated mouse hearts. BCKAs protected cardiomyocytes from oxidative stress-induced cell death in vitro. Mechanistically, BCKA protected oxidative stress induced cell death by inhibiting necrosis without affecting apoptosis or autophagy. Furthermore, BCKAs, but not BCAAs, protected mitochondria and energy production from oxidative injury. Finally, admini

SUBMITTER: Dong W 

PROVIDER: S-EPMC5174097 | biostudies-literature | 2016 Dec

REPOSITORIES: biostudies-literature