Modulation of the transducer function of Na⁺,K⁺-ATPase: new mechanism of heart remodeling

Abstract

Endogenous digitalis-like factors were found in the mammalian and human blood. It was the starting point for the elucidation of the new non-pumping function of the Na,K-ATPase. It was previously well known that Na,K-ATPase is a pharmacological target receptor for cardiac glycosides (J.C. Skou. 1957. Biochim. Biophys. Acta, 23: 394-401). We have investigated the trophotropic effects of such agents as ouabain, epinephrine, norepinephrine, atenolol, and comenic acid using the organotypic tissue culture combined with the reconstruction of optical cross sections and confocal microscopy. It was shown that the growth zone of organotypic culture forms a multidimensional structure. Our results indicate that the cardiac glycoside ouabain applied in endogenous concentrations (10, 10 mol/L) can modulate transducer function of Na,K-ATPase and control the cell growth and proliferation. It was also shown that Src-kinase is involved in "endogenous" ouabain activated intracellular pathways as a series unit. Epinephrine (10-10 mol/L) and comenic acid (10-10 mol/L) were demonstrated to modulate the growth of 10- to 12-day-old chicken embryo cardiac tissue explants in a dose-dependent manner. Epinephrine and comenic acid regulate growth and proliferation of the cardiac tissue via receptor-mediated modulation Na,K-ATPase as a signal transducer. The trophotropic effects of the investigated agents specifically control the heart remodeling phenomenon.

A Metabolomics-Based Strategy for the Mechanism Exploration of Traditional Chinese Medicine:Descurainia sophiaSeeds Extract and Fractions as a Case Study

“…High level of Phe will promote the secretion of insulin on one hand, which lowers the blood glucose level and results in the insufficient energy supply for cardiomyocyte [ 19 ], and inhibit the activity of Na + , K + -ATPase on the other hand [ 20 ]. Na + , K + -ATPase is essential for the maintenance of cardiac function [ 21 ] and plays a key role in the regulation of cardiovascular function [ 22 ]. It provides energy for myocardial contraction and relaxation and maintains the balance of sodium and potassium ion.…”

On the Many Actions of Ouabain: Pro-Cystogenic Effects in Autosomal Dominant Polycystic Kidney Disease

“…Among the effects of relatively low ouabain concentrations, original studies showed that ouabain can promote growth of myocardiocytes [ 56 , 57 ]. Moreover, in the whole heart, ouabain induces cardiac remodeling and has beneficial effects in ischemia/reperfusion injury in what is called ouabain preconditioning [ 58 , 59 , 60 ]. Ouabain dependent cell proliferation has also been found in other cell types, including human umbilical vein endothelial cells (HUVEC) [ 61 ], bovine, canine, and rat vascular smooth muscle cells [ 62 , 63 , 64 ].…”