Skip to main content
Journal cover image

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

Publication ,  Journal Article
Dong, W; Zhou, M; Dong, M; Pan, B; Liu, Y; Shao, J; Gu, X; Huang, Y; Li, G; Wang, Y; Sun, H
Published in: J Mol Cell Cardiol
December 2016

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.

Duke Scholars

Published In

J Mol Cell Cardiol

DOI

EISSN

1095-8584

Publication Date

December 2016

Volume

101

Start / End Page

90 / 98

Location

England

Related Subject Headings

  • Oxidative Stress
  • Necrosis
  • Myocytes, Cardiac
  • Myocardial Reperfusion Injury
  • Mitochondria
  • Mice
  • Keto Acids
  • Humans
  • Energy Metabolism
  • Disease Models, Animal
 

Citation

APA
Chicago
ICMJE
MLA
NLM
Dong, W., Zhou, M., Dong, M., Pan, B., Liu, Y., Shao, J., … Sun, H. (2016). Keto acid metabolites of branched-chain amino acids inhibit oxidative stress-induced necrosis and attenuate myocardial ischemia-reperfusion injury. J Mol Cell Cardiol, 101, 90–98. https://doi.org/10.1016/j.yjmcc.2016.11.002
Dong, Weibing, Meiyi Zhou, Mei Dong, Bangfen Pan, Yunxia Liu, Jing Shao, Xiaoping Gu, et al. “Keto acid metabolites of branched-chain amino acids inhibit oxidative stress-induced necrosis and attenuate myocardial ischemia-reperfusion injury.J Mol Cell Cardiol 101 (December 2016): 90–98. https://doi.org/10.1016/j.yjmcc.2016.11.002.
Dong, Weibing, et al. “Keto acid metabolites of branched-chain amino acids inhibit oxidative stress-induced necrosis and attenuate myocardial ischemia-reperfusion injury.J Mol Cell Cardiol, vol. 101, Dec. 2016, pp. 90–98. Pubmed, doi:10.1016/j.yjmcc.2016.11.002.
Dong W, Zhou M, Dong M, Pan B, Liu Y, Shao J, Gu X, Huang Y, Li G, Wang Y, Sun H. Keto acid metabolites of branched-chain amino acids inhibit oxidative stress-induced necrosis and attenuate myocardial ischemia-reperfusion injury. J Mol Cell Cardiol. 2016 Dec;101:90–98.
Journal cover image

Published In

J Mol Cell Cardiol

DOI

EISSN

1095-8584

Publication Date

December 2016

Volume

101

Start / End Page

90 / 98

Location

England

Related Subject Headings

  • Oxidative Stress
  • Necrosis
  • Myocytes, Cardiac
  • Myocardial Reperfusion Injury
  • Mitochondria
  • Mice
  • Keto Acids
  • Humans
  • Energy Metabolism
  • Disease Models, Animal