The Redox-Sensitive Na/K-ATPase Signaling in Uremic Cardiomyopathy

Int J Mol Sci. 2020 Feb 13;21(4):1256. doi: 10.3390/ijms21041256.

Abstract

In recent years, Na/K-ATPase signaling has been implicated in different physiological and pathophysiological conditions, including cardiac hypertrophy and uremic cardiomyopathy. Cardiotonic steroids (CTS), specific ligands of Na/K-ATPase, regulate its enzymatic activity (at higher concentrations) and signaling function (at lower concentrations without significantly affecting its enzymatic activity) and increase reactive oxygen species (ROS) generation. On the other hand, an increase in ROS alone also regulates the Na/K-ATPase enzymatic activity and signaling function. We termed this phenomenon the Na/K-ATPase-mediated oxidant-amplification loop, in which oxidative stress regulates both the Na/K-ATPase activity and signaling. Most recently, we also demonstrated that this amplification loop is involved in the development of uremic cardiomyopathy. This review aims to evaluate the redox-sensitive Na/K-ATPase-mediated oxidant amplification loop and uremic cardiomyopathy.

Keywords: Na/K-ATPase; c-Src. ROS; partial (5/6th) nephrectomy; signaling; uremic cardiomyopathy.

Publication types

  • Review

MeSH terms

  • Cardiac Glycosides / therapeutic use
  • Cardiomyopathies / drug therapy
  • Cardiomyopathies / etiology
  • Cardiomyopathies / genetics*
  • Cardiomyopathies / pathology
  • Humans
  • Oxidation-Reduction
  • Oxidative Stress / genetics*
  • Reactive Oxygen Species / metabolism
  • Signal Transduction
  • Sodium-Potassium-Exchanging ATPase / antagonists & inhibitors
  • Sodium-Potassium-Exchanging ATPase / genetics*
  • Uremia / complications
  • Uremia / drug therapy
  • Uremia / genetics*
  • Uremia / pathology

Substances

  • Cardiac Glycosides
  • Reactive Oxygen Species
  • Sodium-Potassium-Exchanging ATPase