N 6 -(2-Hydroxyethyl) adenosine prevents myocardial ischemia/reperfusion injury and restores autophagic flux by activating adenosine A1 receptor

// Sisi Zhang 1 , Yiqiu Chai 1, 2 , Ming Fang 2 , Mengli Zhang 2 , Yougao Liu 2 , Bichun Zhu 1 , Weijian Zhu 1 and Xiaola Li 2 1 Wenzhou Medical University, Wenzhou 325027, China 2 Wenzhou Key Research and Development Laboratory of Entomogenous Fungus Resources, Institute of Subtropical Crops, Zhejiang Academy of Agricultural Sciences, Wenzhou 325005, China Correspondence to: Yiqiu Chai, email: chai-yiqiu@yeah.net Keywords: LC3; p62; H9C2; autophagy; cardioprotection Received: August 02, 2017      Accepted: November 14, 2017      Published: January 02, 2018 ABSTRACT Ischemia/reperfusion(I/R) accounts for a great part of the myocardial injury occurring with ischemic heart disease and no standard therapies are available targeting I/R injury. Since the nucleoside adenosine has been shown to mimic both early and late phase ischemic preconditioning. Here, we tested the hypothesis that N 6 -(2-Hydroxyethyl) adenosine(HEA), an adenosine analogues in the medicinal mushroom Ophiocordyceps sobolifera , will active adenosine A1 receptor (AA1R) to blunt I/R injury. The results showed that HEA lighten I/R injury with improved cardiac function, decreased infarct size, apoptosis, histopathological injury and inflammatory in vivo . HEA increased LC3-II and p62 both in vivo and in vitro , and improved cell viability, restored autophagic flux in vitro . The cardioprotection and repairing autophagic flux effect byHEA could destroy by AA1R antagonist DPCPX. Overall, activating AA1R by HEA plays a role of cardioprotection and restoring autophagic flux.