Activation of Na＋/K＋-ATPase attenuates high glucose-induced H9c2 cell apoptosis via suppressing ROS accumulation and MAPKs activities bv DRm217

Hyperglycemia is one of the major factors responsible for the myocardial apoptosis and dysfunc- tion in diabetes. Many studies have proved that there is a close relationship between decreased Na＋/K＋-ATPase activity and diabetic cardiomyopathy. However, the effect of directly activated Na＋/K＋-ATPase on high glucose-induced myocardial injury is still unknown. Here we found that DRm217, a Na＋/K＋-ATPase＇s DR-region specific monoclonal antibody and direct activator, could prevent high glucose-induced H9c2 cell injury, reactive oxygen species （ROS） release, and mito- chondrial dysfunction. High glucose-treatment decreased Na＋/K＋-ATPase activity and increased intracellular Ca2＋ level, whereas DRm217 increased Na＋/K＋-ATPase activity and alleviated Ca2＋ overload. Inhibition of Ca2＋ overload or closing sodium calcium exchanger （NCX channel） could reverse high glucose-induced ROS increasing and cell injury. In addition, DRm217 could signifi- cantly attenuate high glucose-induced p38, JNK and ERK1/2 phosphorylation, which were involved in high glucose-induced cell injury and ROS accumulation. Our findings suggest that DRm217 may protect against the deleterious effects of high glucose in the heart. Prevention of high glucose-induced myocardial cell injury by specific Na＋/K＋-ATPase activator may be an attractive therapeutic option.