Targeting Na/K-ATPase Signaling: A New Approach to Control Oxidative Stress

Renal and cardiac function are greatly affected by chronic oxidative stress which can cause many pathophysiological states. The Na/K-ATPase is well-described as an ion pumping enzyme involved in maintaining cellular ion homeostasis; however, in the past two decades, extensive research has been done to understand the signaling function of the Na/K-ATPase and determine its role in physiological and pathophysiological states. Our lab has shown that the Na/K-ATPase signaling cascade can function as an amplifier of reactive oxygen species (ROS) which can be initiated by cardiotonic steroids or increases in ROS. Regulation of systemic oxidative stress by targeting Na/K-ATPase signaling mediated oxidant amplification improves 5/6th partial nephrectomy (PNx) mediated uremic cardiomyopathy, renal sodium handling, as well as ameliorates adipogenesis. This review will present this new concept of Na/K-ATPase signaling mediated oxidant amplification loop and its clinic implication.