Adiponectin exerts cardioprotection against ischemia/reperfusion injury partially via calreticulin mediated anti-apoptotic and anti-oxidative actions

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• 作者：Yang Sun ; Dajun Zhao ; Yang Yang ; Chao Gao ; Xing Zhang ; Zhiqiang Ma…
• 关键词：Adiponectin ; Apoptosis ; Calreticulin ; Myocardial ischemia/reperfusion ; Oxidative stress
• 刊名：Apoptosis
• 出版年：2017
• 出版时间：January 2017
• 年：2017
• 卷：22
• 期：1
• 页码：108-117
• 全文大小：
• 刊物类别：Medicine
• 刊物主题：Cancer Research; Cell Biology; Oncology; Biochemistry, general; Virology;
• 出版者：Springer US
• ISSN：1573-675X
• 卷排序：22

文摘

The underlying mechanisms of cardioprotection of adiponectin (APN) against ischemia/reperfusion (I/R) injury remain largely unknown. The present study aimed to investigate whether calreticulin (CRT) mediated APN’s cardioprotection against I/R injury. We inhibited mice cardiac CRT expression via intra-myocardial injection of CRT SiRNA, performed transient LAD ligation, measured the cardiac function, apoptosis and oxidative stress to identify CRT’s effects on cardioprotective actions of APN against I/R injury in vivo. LDH release and expression of CRT were measured in neonatal cardiomyocytes (NCM) subjected to simulated I/R (SI/R) and APN. CRT specific SiRNA was also utilized in vitro. CRT inhibition partially blunted cardioprotection of APN against I/R injury (evidenced by left ventricular ejection fraction and myocardial infarct size). It also blunted APN’s function against I/R induced apoptosis and oxidative stress (evidenced by TUNEL positive staining and reactive oxygen species production). In addition, SI/R increased LDH release, and administration of APN attenuated SI/R-induced cell death significantly. However, neither SI/R nor APN altered CRT expression in NCM. Inhibition of CRT expression blunted cardioprotective action of APN against SI/R induced apoptotic events (evidenced by TUNEL positive staining, LDH release and Caspase 3 activity). Furthermore, CRT inhibition significantly blunted APN’s anti-oxidative action (evidenced by gp91phox expression and superoxide generation). However, CRT inhibition did not attenuate AMPK phosphorylation by APN administration in NCM. Therefore, these novel findings strongly indicate that APN exerts cardioprotective effects against I/R injury partially via CRT mediated anti-apoptotic and anti-oxidative actions.