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UCP2 protect the heart from myocardial ischemia/reperfusion injury via induction of mitochondrial autophagy
Author(s) -
Wu Hui,
Ye Ming,
Liu Di,
Yang Jian,
Ding Jiawang,
Zhang Jing,
Wang Xinan,
Dong Wusong,
Fan Zhixing,
Yang Jun
Publication year - 2019
Publication title -
journal of cellular biochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.028
H-Index - 165
eISSN - 1097-4644
pISSN - 0730-2312
DOI - 10.1002/jcb.28812
Subject(s) - mitophagy , autophagy , mitochondrion , gene knockdown , cardioprotection , ischemia , reperfusion injury , microbiology and biotechnology , downregulation and upregulation , gene silencing , mitochondrial ros , ischemic preconditioning , biology , pharmacology , chemistry , medicine , apoptosis , biochemistry , gene
Abstract Uncoupling protein 2 (UCP2), located in the mitochondrial inner membrane, is a predominant isoform of UCP that expressed in the heart and other tissues of human and rodent tissues. Nevertheless, its functional role during myocardial ischemia/reperfusion (I/R) is not entirely understood. Ischemic preconditioning (IPC) remarkably improved postischemic functional recovery followed by reduced lactate dehydrogenase (LDH) release with simultaneous upregulation of UCP2 in perfused myocardium. We then investigated the role of UCP2 in IPC‐afforded cardioprotective effects on myocardial I/R injury with adenovirus‐mediated in vivo UCP2 overexpression (AdUCP2) and knockdown (AdshUCP2). IPC‐induced protective effects were mimicked by UCP2 overexpression, while which were abolished with silencing UCP2. Mechanistically, UCP2 overexpression significantly reinforced I/R‐induced mitochondrial autophagy (mitophagy), as measured by biochemical hallmarks of mitochondrial autophagy. Moreover, primary cardiomyocytes infected with AdUCP2 increased simulated ischemia/reperfusion (sI/R)‐induced mitophagy and therefore reversed impaired mitochondrial function. Finally, suppression of mitophagy with mdivi‐1 in cultured cardiomyocytes abolished UCP2‐afforded protective effect on sI/R‐induced mitochondrial dysfunction and cell death. Our data identify a critical role for UCP2 against myocardial I/R injury through preventing the mitochondrial dysfunction through reinforcing mitophagy. Our findings reveal novel mechanisms of UCP2 in the cardioprotective effects during myocardial I/R.