Cardiotonic Steroids and Cardiac Fibrosis

Vetteth, Sandeep; Malhotra, Deepak; Shapiro, Joseph I.

doi:10.5772/27204

Cited by 1 publication

(1 citation statement)

References 114 publications

(127 reference statements)

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“…Therefore, we have not fully appreciated CTS's potential effects on cardiac structure and remodeling by affecting cells. Recent studies with transgenic animals and using tools that either increase or block NKA-mediated signal transduction have generated a large body of evidence for an important role of NKA in the regulation of cardiac remodeling (Elkareh et al, 2007;Kometiani et al, 2000;Vetteth et al, 2012;Wansapura et al, 2010;Xie et al, 1999). However, although it is now well accepted that NKA has an ion-pumping independent signaling function, it is still debated whether direct and conformation-dependent NKA/effector interaction is a key to this function.…”

Section: Discussionmentioning

confidence: 99%

Biased Effect of Cardiotonic Steroids on Na/K-ATPase–Mediated Signal Transduction

Marck

Huang

et al. 2021

Mol Pharmacol

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Recent studies have revealed that Na/K-ATPase (NKA) can transmit signals through ion pumping-independent activation of pathways relayed by distinct intracellular protein/lipid kinases and endocytosis challenges the traditional definition that cardiotonic steroids (CTS) is NKA inhibitor. While additional effects of CTS have long been suspected, revealing its agonist impact through the NKA receptor could be a novel mechanism in understanding the basic biology of NKA. In this study, we tested whether different structural CTS could trigger different sets of NKA/effector interactions, resulting in biased signaling responses without compromising ion-pumping capacity. Using purified NKA, we found that ouabain, digitoxigenin, and somalin cause comparable levels of NKA inhibition. However, while endogenous ouabain stimulates both protein kinases This article has not been copyedited and formatted. The final version may differ from this version.

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Section: Discussionmentioning

confidence: 99%