Melatonin receptor-mediated protection against myocardial ischemia/reperfusion injury: role of SIRT1.

Abstract

Melatonin confers cardioprotective effect against myocardial ischemia/reperfusion (MI/R) injury by reducing oxidative stress. Activation of silent information regulator 1 (SIRT1) signaling also reduces MI/R injury. We hypothesize that melatonin may protect against MI/R injury by activating SIRT1 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 SIRT1 inhibitor EX527 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 SIRT1, Bcl-2 expression and downregulating Bax, 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 EX527 or luzindole, indicating that SIRT1 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 SIRT1 signaling in a receptor-dependent manner.

• Authors: Liming Yu, Yang Sun, Liang Cheng, Zhenxiao Jin, Yang Yang, Mengen Zhai, Haifeng Pei, Xiaowu Wang, Haifeng Zhang, Qiang Meng, Yu Zhang, Shiqiang Yu, Weixun Duan
• Journal: Journal of pineal research (J Pineal Res) Vol. 57 Issue 2 Pg. 228-38 (Sep 2014) ISSN: 1600-079X [Electronic] England
• PMID: 25052362 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Chemical References

• 6-chloro-2,3,4,9-tetrahydro-1H-carbazole-1-carboxamide
• Carbazoles
• Receptors, Melatonin
• Tryptamines
• luzindole
• L-Lactate Dehydrogenase
• Superoxide Dismutase
• Caspase 3
• Sirt1 protein, rat
• Sirtuin 1
• Melatonin

Topics

• Animals
• Apoptosis (drug effects)
• Carbazoles (pharmacology)
• Caspase 3 (metabolism)
• L-Lactate Dehydrogenase (metabolism)
• Male
• Melatonin (therapeutic use)
• Myocardial Reperfusion Injury (prevention & control)
• Myocardium (metabolism)
• Oxidative Stress (drug effects)
• Rats
• Rats, Sprague-Dawley
• Receptors, Melatonin (metabolism)
• Signal Transduction (drug effects)
• Sirtuin 1 (antagonists & inhibitors, metabolism)
• Superoxide Dismutase (metabolism)
• Tryptamines (pharmacology)