Adiponectin exerts cardioprotection against ischemia/reperfusion injury partially via calreticulin mediated anti-apoptotic and anti-oxidative actions
Adiponectin exerts cardioprotection against ischemia/reperfusion injury partially via calreticulin mediated anti-apoptotic and anti-oxidative actions
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脂联素部分通过钙网蛋白介导的抗凋亡和抗氧化作用对缺血/再灌注损伤发挥心脏保护作用
DOI：
10.1007/s10495-016-1304-8
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发表时间：
2017-01-01
期刊：
影响因子：
7.2
通讯作者：
Gao, Feng
中科院分区：
文献类型：
--
作者：
Sun, Yang;Zhao, Dajun;Gao, Feng
脂联素（APN）对缺血/再灌注（I/R）损伤的心脏保护的潜在机制仍然很大程度上未知。本研究旨在探讨钙网蛋白（CRT）是否介导APN对I/R损伤的心脏保护作用。我们通过心肌内注射CRT SiRNA抑制小鼠心脏CRT的表达，进行短暂LAD结扎，测量心功能、细胞凋亡和氧化应激，以确定CRT对体内APN对I/R损伤的心脏保护作用。在模拟I/R （SI/R）和APN作用下，测定新生儿心肌细胞（NCM） LDH的释放和CRT的表达。CRT特异性SiRNA也被用于体外。CRT抑制部分减弱了APN对I/R损伤的心脏保护作用（由左心室射血分数和心肌梗死面积证明）。APN对I/R诱导的细胞凋亡和氧化应激的抑制作用也减弱（通过TUNEL阳性染色和活性氧产生证实）。此外，SI/R增加了LDH的释放，APN的施用显著减轻了SI/R诱导的细胞死亡。然而，SI/R和APN均未改变NCM中CRT的表达。抑制CRT表达减弱了APN对SI/R诱导的凋亡事件的心脏保护作用（通过TUNEL阳性染色、LDH释放和Caspase 3活性证明）。此外，CRT抑制显著减弱了APN的抗氧化作用（gp91（phox）表达和超氧化物生成证明）。然而，CRT抑制并没有减弱NCM中APN的AMPK磷酸化。因此，这些新发现强烈表明APN部分通过CRT介导的抗凋亡和抗氧化作用对I/R损伤发挥心脏保护作用。
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 gp91(phox) 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.