Activation of Na-K-ATPase with DRm217 attenuates oxidative stress-induced myocardial cell injury via closing Na-K-ATPase/Src/Ros amplifier.

Reduced Na-K-ATPase activity has close relationship with cardiomyocyte death. Reactive oxygen species (ROS) also plays an important role in cardiac cell damage. It has been proved that Na-K-ATPase and ROS form a feed-forward amplifier. The aim of this study was to explore whether DRm217, a proved Na/K-ATPase's DR-region specific monoclonal antibody and direct activator, could disrupt Na-K-ATPase/ROS amplifier and protect cardiac cells from ROS-induced injury. We found that DRm217 protected myocardial cells against hydrogen peroxide (HO)-induced cardiac cell injury and mitochondrial dysfunction. DRm217 also alleviated the effect of HO on inhibition of Na-K-ATPase activity, Na-K-ATPase cell surface expression, and Src phosphorylation. HO-treatment increased intracellular ROS, mitochondrial ROS and induced intracellular Ca, mitochondrial Ca overload. DRm217 closed Na-K-ATPase/ROS amplifier, alleviated Ca accumulation and finally inhibited ROS and mitochondrial ROS generation. These novel results may help us to understand the important role of the Na-K-ATPase in oxidative stress and oxidative stress-related disease.