Effects of PP2A/Nrf2 on experimental diabetes mellitus-related cardiomyopathy by regulation of autophagy and apoptosis through ROS dependent pathway.

Diabetes mellitus-related cardiomyopathy (DMCMP) has been defined as ventricular dysfunction that occurs in diabetic patients independent of a recognized cause such as coronary artery disease or hypertension. Mechanisms underlying DMCMP have not been fully elucidated. In this study, the roles of protein phosphatase 2A/nuclear factor NF-E2-related factor 2 (PP2A/Nrf2) in experimental DMCMP induced by high glucose were studied in vitro and in vivo. The results showed that high glucose could induce experimental DMCMP and increase ROS generation, increase the expression and nuclear translocation of Nrf2, down-regulate the expression of PI3K/Akt/mTOR and up-regulate the expression of ERK, and activate the autophagy of cardiomyocytes. The activity or expression of PP2A in DMCMP increased. PP2A could up-regulate the expression of Nrf2 and promote cardiomyocytes autophagy and apoptosis. Inhibition of PP2A could reduce the expression of Nrf2 and inhibit the autophagy and apoptosis of cardiomyocytes. The results suggested that hyperglycemic-induced experimental DMCMP may be related to up-regulating the expression of Nrf2 through PP2A/Nrf2 pathway. These results will be helpful to elucidate the pathogenesis and mechanism of DMCMP and find targets for the development of new drugs to prevent or treat DMCMP.