Abstract
Na/K-ATPase has been extensively studied for its ion pumping function, but, in the past several decades, has been identified as a scaffolding and signaling protein. Initially it was found that cardiotonic steroids (CTS) mediate signal transduction through the Na/K-ATPase and result in the generation of reactive oxygen species (ROS), which are also capable of initiating the signal cascade. However, in recent years, this Na/K-ATPase/ROS amplification loop has demonstrated significance in oxidative stress related disease states, including obesity, atherosclerosis, heart failure, uremic cardiomyopathy, and hypertension. The discovery of this novel oxidative stress signaling pathway, holds significant therapeutic potential for the aforementioned conditions and others that are rooted in ROS.
Highlights
The Na/K-ATPase enzyme (“sodium pump”) is well known for its ion pumping function, but was discovered to have a scaffolding and signaling function by Dr Zijian Xie in the late1990s
Studies in mouse models of obesity have shown that the production of reactive oxygen species (ROS) increases selectively in white adipose tissue (WAT) of obese mice, suggesting that in obesity, increased oxidative stress in plasma is due to increased ROS production from accumulated fat [43,46,47]
We demonstrated the ability of the Na/K-ATPase signal cascade to amplify ROS involved in adipogenesis, a process not previously linked to cardiotonic steroids or the Na/K-ATPase signal cascade
Summary
The Na/K-ATPase enzyme (“sodium pump”) is well known for its ion pumping function, but was discovered to have a scaffolding and signaling function by Dr Zijian Xie in the late. Over the last twenty years, studies have shown that this signaling pathway, and alterations with it, is involved with a number of clinical disorders, including cancer, chronic kidney disease, and cardiovascular diseases, such as uremic cardiomyopathy [1,2]. Our recent work with obesity models has provided evidence that the Na/K-ATPase signaling cascade activation worsens obesity, diabetes, dyslipidemia, and atherosclerosis, as these conditions are all related to an imbalance of oxidative stress (Figure 1) [3]. Na/K-ATPase and the signaling pathway present increasing importance, given the therapeutic potential it holds for the aforementioned clinical disorders.
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