Polypeptide Globular Adiponectin Attenuates Hypoxia/Reoxygenation-induced Necroptosis In Cardiomyocytes By The P38MAPK/NF-?B Pathways

Objective:Necroptosis,also known as regulated necrosis,plays an important role in myocardial ischemia/reperfusion injury(MIRI).Globular adiponectin(gAd)is a protein hormone that modulates a number of metabolic processes and plays an important role in cardiovascular homeostasis including protecting cardiomyocytes during MIRI.The protective mechanisms by which gAd affects the cardiomyocytes during hypoxia/reoxygenation conditions are still not clear.We established a myocardial hypoxia/reoxygenation model using SD neonatal rat ventricular myocytes(NRVMs)and aimed to investigate the role of gAd on hypoxia/reoxygenation-induced apoptosis and necroptosis.Methods:Cultured SD neonatal rat ventricular myocytes(NRVMs),which were pretreated with gAd(0.0.5,1,and 2 ?g/ml,24 h),were exposured to hypoxia/reoxygenation conditions and analyzed by using respectively MTT and LDH assays to evaluate the cell viability and the levels of LDH.The ratio between apoptosis and necrosis in NRVMs was distinguished by TUNEL staining.Western blotting was used to assess the expression levels of cleaved caspase3,RIP1,RIP3,p38 MAPK,NF-?B,Bcl-2 and Bax.Oxidative stress was mainly evaluated by the following three aspects : reactive oxygen species(ROS)levels,malonaldehyde(MDA)and superoxide dismutase(SOD)activity.Results:1.gAd attenuated hypoxia/reoxygenation-mediated cardiomyocyte injury by increasing the cellular viability and cell number and reducing the release of LDH.2.gAd could inhibit both necroptosis and apoptosis during hypoxia/reoxygenation.3.gAd attenuated hypoxia/reoxygenation-induced necroptosis and apoptosis by an antioxidative mechanism and by regulating the p38MAPK/NF-?B pathway.Conclusion:gAd inhibits hypoxia/reoxygenation-induced apoptosis and necroptosis in cardiomyocytes by regulating the p38MAPK/NF-?B pathways.