Back to Search
Start Over
Keto acid metabolites of branched-chain amino acids inhibit oxidative stress-induced necrosis and attenuate myocardial ischemia–reperfusion injury
- Source :
- Journal of Molecular and Cellular Cardiology. 101:90-98
- Publication Year :
- 2016
- Publisher :
- Elsevier BV, 2016.
-
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, administration of BCKAs during reperfusion was sufficient to significantly attenuate cardiac I/R injury. These findings uncover an unexpected role of BCAAs metabolites in cardioprotection against acute ischemia/reperfusion injury, and demonstrate the potential use of BCKAs treatment to preserve ischemic tissue during reperfusion.
- Subjects :
- 0301 basic medicine
Programmed cell death
Necrosis
Cell Respiration
Myocardial Reperfusion Injury
Oxidative phosphorylation
030204 cardiovascular system & hematology
Mitochondrion
Pharmacology
Biology
medicine.disease_cause
Article
Cell Line
Mice
03 medical and health sciences
0302 clinical medicine
medicine
Animals
Humans
Myocytes, Cardiac
Molecular Biology
Cardioprotection
Cell Death
Autophagy
medicine.disease
Keto Acids
Mitochondria
Disease Models, Animal
Oxidative Stress
030104 developmental biology
Biochemistry
medicine.symptom
Energy Metabolism
Cardiology and Cardiovascular Medicine
Reperfusion injury
Amino Acids, Branched-Chain
Oxidative stress
Subjects
Details
- ISSN :
- 00222828
- Volume :
- 101
- Database :
- OpenAIRE
- Journal :
- Journal of Molecular and Cellular Cardiology
- Accession number :
- edsair.doi.dedup.....e70cbb6b48f1150112c0eb788674f770