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Melatonin receptor‐mediated protection against myocardial ischemia/reperfusion injury: role of SIRT 1
Author(s) -
Yu Liming,
Sun Yang,
Cheng Liang,
Jin Zhenxiao,
Yang Yang,
Zhai Mengen,
Pei Haifeng,
Wang Xiaowu,
Zhang Haifeng,
Meng Qiang,
Zhang Yu,
Yu Shiqiang,
Duan Weixun
Publication year - 2014
Publication title -
journal of pineal research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.881
H-Index - 131
eISSN - 1600-079X
pISSN - 0742-3098
DOI - 10.1111/jpi.12161
Subject(s) - luzindole , melatonin , melatonin receptor , oxidative stress , superoxide dismutase , malondialdehyde , cardioprotection , endocrinology , reperfusion injury , medicine , signal transduction , receptor , pharmacology , chemistry , ischemia , biochemistry
Abstract Melatonin confers cardioprotective effect against myocardial ischemia/reperfusion ( MI / R ) injury by reducing oxidative stress. Activation of silent information regulator 1 ( SIRT 1) signaling also reduces MI / R injury. We hypothesize that melatonin may protect against MI / R injury by activating SIRT 1 signaling. This study investigated the protective effect of melatonin treatment on MI / R heart and elucidated its potential mechanisms. Rats were exposed to melatonin treatment in the presence or the absence of the melatonin receptor antagonist luzindole or SIRT 1 inhibitor EX 527 and then subjected to MI / R operation. Melatonin conferred a cardioprotective effect by improving postischemic cardiac function, decreasing infarct size, reducing apoptotic index, diminishing serum creatine kinase and lactate dehydrogenase release, upregulating SIRT 1, B cl‐2 expression and downregulating B ax, caspase‐3 and cleaved caspase‐3 expression. Melatonin treatment also resulted in reduced myocardium superoxide generation, gp91 phox expression, malondialdehyde level, and increased myocardium superoxide dismutase ( SOD ) level, which indicate that the MI / R ‐induced oxidative stress was significantly attenuated. However, these protective effects were blocked by EX 527 or luzindole, indicating that SIRT 1 signaling and melatonin receptor may be specifically involved in these effects. In summary, our results demonstrate that melatonin treatment attenuates MI / R injury by reducing oxidative stress damage via activation of SIRT 1 signaling in a receptor‐dependent manner.