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Insulin suppresses ischemia/reperfusion‐induced myocardial injury via inhibiting mitochondrial JNK translocation (547.20)
Author(s) -
Xu Jie,
Qin Xinghua,
Zhang Xing,
Yang Lu,
Xing Yuan,
Gao Feng
Publication year - 2014
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.28.1_supplement.547.20
Subject(s) - cardioprotection , mitochondrion , cytochrome c , insulin , reperfusion injury , cytosol , apoptosis , tunel assay , medicine , chromosomal translocation , ischemia , myocardial infarction , endocrinology , pharmacology , chemistry , biology , microbiology and biotechnology , biochemistry , gene , enzyme
Objective: Insulin exerts cardioprotective effect against ischemia/reperfusion (I/R) injury, but the underlying mechanism is unclear. This study aimed to examine the role of mitochondria in insulin‐induced cardioprotection against myocardial I/R injury. Methods: Adult male rats were subjected to 30 min of myocardial ischemia and 2 h of reperfusion. Rats randomly received vehicle, insulin, and Tat‐Sab KIM1 administered 5 min before reperfusion. Incidence of myocardial apoptosis was determined by TUNEL. JNK from the extractions of mitochondria, cytosol/nucleus, and whole cell was detected by Western blot. Results: Myocardial I/R produced significant myocardial apoptosis, both mitochondrial and cytosolic/nuclear JNK activation and myocardial infarction (n=6, P<0.05). Importantly, we found JNK translocation from mitochondria to cytosol/nucleus together with cytochrome c release following myocardial I/R, which were blunted by insulin treatment. Inhibiting JNK translocation to mitochondria with Tat‐Sab KIM1 , a retro‐inverso peptide which disrupting the JNK interaction with mitochondria, not only decreased mitochondrial JNK activation but also exerted cardioprotective effect as evidenced by reduced myocardial apoptosis (10.2±1.3% vs . 16.0±1.2%, P<0.05) and myocardial infarct size (15.9±2.1% vs. 23.7±1.5%, P<0.05) after myocardial I/R. Conclusion: These data show that insulin exerts mitochondrial protective action via disrupting JNK translocation to mitochondria and thus inhibiting cytochrome c release, which contributes to insulin‐elicited cardioprotection against I/R injury. Key words: insulin, ischemia/reperfusion injury, JNK signaling, mitochondria, cardioprotection Grant Funding Source : supported by grants from the National Basic Research Program of China (No. 2013CB531204)