Melatonin receptor‐mediated protection against myocardial ischemia/reperfusion injury: role of <scp>SIRT</scp>1

<jats:title>Abstract</jats:title><jats:p>Melatonin confers cardioprotective effect against myocardial ischemia/reperfusion (<jats:styled-content style="fixed-case">MI</jats:styled-content>/<jats:styled-content style="fixed-case">R</jats:styled-content>) injury by reducing oxidative stress. Activation of silent information regulator 1 (<jats:styled-content style="fixed-case">SIRT</jats:styled-content>1) signaling also reduces <jats:styled-content style="fixed-case">MI</jats:styled-content>/<jats:styled-content style="fixed-case">R</jats:styled-content> injury. We hypothesize that melatonin may protect against <jats:styled-content style="fixed-case">MI</jats:styled-content>/<jats:styled-content style="fixed-case">R</jats:styled-content> injury by activating <jats:styled-content style="fixed-case">SIRT</jats:styled-content>1 signaling. This study investigated the protective effect of melatonin treatment on <jats:styled-content style="fixed-case">MI</jats:styled-content>/<jats:styled-content style="fixed-case">R</jats:styled-content> 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 <jats:styled-content style="fixed-case">SIRT</jats:styled-content>1 inhibitor <jats:styled-content style="fixed-case">EX</jats:styled-content>527 and then subjected to <jats:styled-content style="fixed-case">MI</jats:styled-content>/<jats:styled-content style="fixed-case">R</jats:styled-content> 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 <jats:styled-content style="fixed-case">SIRT</jats:styled-content>1, <jats:styled-content style="fixed-case">B</jats:styled-content>cl‐2 expression and downregulating <jats:styled-content style="fixed-case">B</jats:styled-content>ax, caspase‐3 and cleaved caspase‐3 expression. Melatonin treatment also resulted in reduced myocardium superoxide generation, gp91<jats:sup>phox</jats:sup> expression, malondialdehyde level, and increased myocardium superoxide dismutase (<jats:styled-content style="fixed-case">SOD</jats:styled-content>) level, which indicate that the <jats:styled-content style="fixed-case">MI</jats:styled-content>/<jats:styled-content style="fixed-case">R</jats:styled-content>‐induced oxidative stress was significantly attenuated. However, these protective effects were blocked by <jats:styled-content style="fixed-case">EX</jats:styled-content>527 or luzindole, indicating that <jats:styled-content style="fixed-case">SIRT</jats:styled-content>1 signaling and melatonin receptor may be specifically involved in these effects. In summary, our results demonstrate that melatonin treatment attenuates <jats:styled-content style="fixed-case">MI</jats:styled-content>/<jats:styled-content style="fixed-case">R</jats:styled-content> injury by reducing oxidative stress damage via activation of <jats:styled-content style="fixed-case">SIRT</jats:styled-content>1 signaling in a receptor‐dependent manner.</jats:p>