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

AbstractThe 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 i njury 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 ejectio n 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 signific antly blunted APN’s anti-oxidative action (evidenced by gp91phox expression...
Source: Apoptosis - Category: Molecular Biology Source Type: research