Adiponectin protects HL-1 cardiomyocytes against rotenone-induced cytotoxicity through AMPK activation.

The relationship between mitochondrial dysfunction or ER stress with pathogenesis of cardiovascular disease is well documented, but the crosstalk between them in cardiovascular diseases is not clear. Adiponectin (APN) is reported to become a potential cardioprotective molecule, but whether and how APN regulates mitochondrial dysfunction and ER stress is not clear. In this study, we used rotenone-treated HL-1 atrial cardiomyocytes as an in vitro model of mitochondrial dysfunction to investigate the possible interactions between mitochondrial dysfunction and ER stress and explore the effects of APN on rotenone-induced cytotoxicity and the underlying mechanisms. It found that rotenone treatment significantly activated the ER stress PRK-like endoplasmic reticulum kinase (PERK)-dependent pathway, decreased autophagic flux and APN expression in a dose-dependent manner. Pretreatment of GSK2606414, an inhibitor of PERK kinase activity, attenuated the rotenone-induced decrease of APN expression. In return exogenous APN pretreatment inhibited rotenone-induced ER stress and activated autophagy via AMP-activated protein kinase (AMPK) activation and protected HL-1 cells against apoptosis and enhanced the viability after rotenone treatment. In conclusion, rotenone treatment induced significant cardiomyocyte cytotoxicity and ER stress, suppressed autophagy, and decreased APN expression in HL-1 cells. APN in return inhibited ER stress and activated autophagy through AMPK activation, thus alleviating rotenone induced HL-1 apoptosis.