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Molecules 2017, 22(4), 635;

Na+i,K+i-Dependent and -Independent Signaling Triggered by Cardiotonic Steroids: Facts and Artifacts

Laboratory of Biological Membranes, Faculty of Biology, M.V. Lomonosov Moscow State University, 1/12 Leninskie Gory, Moscow 119234, Russia
Department of Medical Biology, Siberian Medical State University, Tomsk 634055, Russia
Department of Sports Tourism Sports Physiology and Medicine, National Research Tomsk State University, Tomsk 634050, Russia
Author to whom correspondence should be addressed.
Academic Editor: Robert Kiss
Received: 23 February 2017 / Revised: 31 March 2017 / Accepted: 11 April 2017 / Published: 14 April 2017
(This article belongs to the Special Issue Cardiotonic Steroids)
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Na+,K+-ATPase is the only known receptor of cardiotonic steroids (CTS) whose interaction with catalytic α-subunits leads to inhibition of this enzyme. As predicted, CTS affect numerous cellular functions related to the maintenance of the transmembrane gradient of monovalent cations, such as electrical membrane potential, cell volume, transepithelial movement of salt and osmotically-obliged water, symport of Na+ with inorganic phosphate, glucose, amino acids, nucleotides, etc. During the last two decades, it was shown that side-by-side with these canonical Na+i/K+i-dependent cellular responses, long-term exposure to CTS affects transcription, translation, tight junction, cell adhesion and exhibits tissue-specific impact on cell survival and death. It was also shown that CTS trigger diverse signaling cascades via conformational transitions of the Na+,K+-ATPase α-subunit that, in turn, results in the activation of membrane-associated non-receptor tyrosine kinase Src, phosphatidylinositol 3-kinase and the inositol 1,4,5-triphosphate receptor. These findings allowed researchers to propose that endogenous CTS might be considered as a novel class of steroid hormones. We focus our review on the analysis of the relative impact Na+i,K+i-mediated and -independent pathways in cellular responses evoked by CTS. View Full-Text
Keywords: cardiotonic steroids; Na+,K+-ATPase; transcription; translation; proliferation; adhesion; cell death cardiotonic steroids; Na+,K+-ATPase; transcription; translation; proliferation; adhesion; cell death

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Orlov, S.N.; Klimanova, E.A.; Tverskoi, A.M.; Vladychenskaya, E.A.; Smolyaninova, L.V.; Lopina, O.D. Na+i,K+i-Dependent and -Independent Signaling Triggered by Cardiotonic Steroids: Facts and Artifacts. Molecules 2017, 22, 635.

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