Keto acid metabolites of branched-chain amino acids inhibit oxidative stress-induced necrosis and attenuate myocardial ischemia-reperfusion injury.
Keto acid metabolites of branched-chain amino acids inhibit oxidative stress-induced necrosis and attenuate myocardial ischemia-reperfusion injury.
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DOI：
10.1016/j.yjmcc.2016.11.002
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发表时间：
2016-12
影响因子：
5
通讯作者：
Sun, Haipeng
中科院分区：
文献类型：
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作者：
Dong, Weibing;Zhou, Meiyi;Dong, Mei;Pan, Bangfen;Liu, Yunxia;Shao, Jing;Gu, Xiaoping;Huang, Ying;Li, Guangping;Wang, Yibin;Sun, Haipeng
关键词：
支链α-酮酸（BCKAs）是支链氨基酸（BCAAs）的内源性代谢产物。BCAA和BCKA在病理性应激心脏中显著升高，并有助于慢性病理性重塑和功能障碍。然而，它们对急性心脏损伤的直接影响尚不清楚。在这里，我们证明了升高的BCKAs显着减弱缺血再灌注（I/R）损伤和保存后I/R功能在离体小鼠心脏。BCKAs在体外保护心肌细胞免受氧化应激诱导的细胞死亡。在机制上，BCKA通过抑制坏死而不影响凋亡或自噬来保护氧化应激诱导的细胞死亡。此外，BCKAs，而不是BCAAs，保护线粒体和能量产生免受氧化损伤。最后，再灌注期间给予BCKAs足以显著减轻心脏I/R损伤。这些发现揭示了BCAA代谢物在心脏保护中对急性缺血/再灌注损伤的意想不到的作用，并证明了BCKAs治疗在再灌注期间保护缺血组织的潜在用途。
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.
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影响因子：
15.9
作者：
Lu, Gang;Sun, Haipeng;Wang, Yibin
通讯作者：
Wang, Yibin
DOI：
10.1016/j.bbadis.2003.09.010
发表时间：
2003-11-20
影响因子：
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影响因子：
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作者：
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通讯作者：
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影响因子：
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作者：
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