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

被引：21

作者：

Dong, Weibing ^{[1
]}

Zhou, Meiyi ^{[1
]}

Dong, Mei ^{[2
]}

Pan, Bangfen ^{[1
]}

Liu, Yunxia ^{[1
]}

Shao, Jing ^{[1
]}

Gu, Xiaoping ^{[1
]}

Huang, Ying ^{[1
]}

Li, Guangping ^{[2
]}

Wang, Yibin ^{[1
,3
,4
,5
]}

Sun, Haipeng ^{[1
,3
,4
,5
]}

机构：

[1] Shanghai Jiao Tong Univ, Key Lab Cell Differentiat & Apoptosis, Dept Pathophysiol, Minist Educ,Sch Med, Shanghai 200025, Peoples R China

[2] Tianjin Med Univ, Tianjin Key Lab Ion Mol Funct Cardiovasc Dis, Tianjin Inst Cardiol, Dept Cardiol,Hosp 2, Tianjin 300211, Peoples R China

[3] Univ Calif Los Angeles, David Geffen Sch Med, Cardiovasc Res Labs, Div Mol Med,Dept Anesthesiol,Mol Biol Inst, Los Angeles, CA 90095 USA

[4] Univ Calif Los Angeles, David Geffen Sch Med, Cardiovasc Res Labs, Div Mol Med,Dept Med,Mol Biol Inst, Los Angeles, CA 90095 USA

[5] Univ Calif Los Angeles, David Geffen Sch Med, Cardiovasc Res Labs, Div Mol Med,Dept Physiol,Mol Biol Inst, Los Angeles, CA 90095 USA

来源：

JOURNAL OF MOLECULAR AND CELLULAR CARDIOLOGY | 2016年 / 101卷

基金：

中国国家自然科学基金;

关键词：

Branched-chain amino acids; Branched-chain keto acids; Necrosis; Cell death; Mitochondria; Myocardial infarction; NECROTIC CELL-DEATH; HYDROGEN-PEROXIDE; ELECTRON-TRANSPORT; SIGNALING PATHWAY; REACTIVE OXYGEN; S-NITROSATION; APOPTOSIS; PROTEIN; KINASE; HEART;

D O I：

10.1016/j.yjmcc.2016.11.002

中图分类号：

R5 [内科学];

学科分类号：

100201 [内科学];

摘要：

Branched chain alpha-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. (C) 2016 Elsevier Ltd. All rights reserved.

引用

页码：90 / 98

页数：9

共 41 条

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Staurosporine induces apoptosis through both caspase-dependent and caspase-independent mechanisms [J].