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

Journal Article (Journal Article)

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, administration of BCKAs during reperfusion was sufficient to significantly attenuate cardiac I/R injury. These findings uncover an unexpected role of BCAA metabolites in cardioprotection against acute ischemia/reperfusion injury, and demonstrate the potential use of BCKA treatment to preserve ischemic tissue during reperfusion.

Full Text

Duke Authors

Cited Authors

  • Dong, W; Zhou, M; Dong, M; Pan, B; Liu, Y; Shao, J; Gu, X; Huang, Y; Li, G; Wang, Y; Sun, H

Published Date

  • December 2016

Published In

Volume / Issue

  • 101 /

Start / End Page

  • 90 - 98

PubMed ID

  • 27832938

Pubmed Central ID

  • PMC5174097

Electronic International Standard Serial Number (EISSN)

  • 1095-8584

Digital Object Identifier (DOI)

  • 10.1016/j.yjmcc.2016.11.002

Language

  • eng

Conference Location

  • England