Reactome | ATP1A:ATP1B:FXYD binds cardiac glycosides

ATP1A:ATP1B:FXYD binds cardiac glycosides

Stable Identifier

R-HSA-9684068

Type

Reaction [binding]

Species

Homo sapiens

Compartment

extracellular region, plasma membrane

ReviewStatus

5/5

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ATP1A:ATP1B:FXYD binds cardiac glycosides

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Cardiac glycosides are a class of organic compounds that increase the output force of the heart and increase its rate of contractions by inhibition of the cellular sodium-potassium ATPase pump (ATP1A1). Their beneficial medical uses are as treatments for congestive heart failure and cardiac arrhythmias. Cardiac glycosides are primarily derived from foxglove plants or from the venom of the cane toad Bufo marinus. Their toxicity prevents them from being widely used. Changes to heart inotropic and chronotropic activity results in multiple kinds of dysrhythmia and potentially fatal ventricular tachycardia. Different cardiac glycosides show different specificities towards sodium-potassium ATPase pump alpha isoforms (Hauck et al. 2009, Katz et al. 2010, Cherniavsky et al. 2015).

HIV-1 Tat is essential for HIV-1 replication. Tat must escape from the cell in order for it to activate the HIV-1 LTR promoter and facilitate HIV-1 viral replication. Tat utilises the cellular ATP1A1 pump for secretion out of cells. The cardiac glycosides ouabain, digoxin, digitoxin, acetyldigitoxin and deslanoside can all inhibit ATP1A1 (Smith 1984), impairing extracellular Tat release and blocking HIV-1 replication (Agostini et al. 2017).

Literature References

PubMed ID	Title	Journal	Year
6328127	The basic mechanism of inotropic action of digitalis glycosides Smith, TW	J Pharmacol	1984
28645727	Inhibition of Non Canonical HIV-1 Tat Secretion Through the Cellular Na⁺,K⁺-ATPase Blocks HIV-1 Infection Tasciotti, E, Fittipaldi, A, Agostini, S, Giacca, M, Ali, H, Vardabasso, C, Lusic, M, Bugatti, A, Cereseto, A, Rusnati, M	EBioMedicine	2017
19751721	Isoform specificity of cardiac glycosides binding to human Na+,K+-ATPase alpha1beta1, alpha2beta1 and alpha3beta1 Wittwer, T, Schwinger, RH, Wahlers, T, Bartz, M, Müller-Ehmsen, J, McDonough, AA, Scheiner-Bobis, G, Potter, T, Hauck, C, Bloch, W, Mehlhorn, U	Eur. J. Pharmacol.	2009
25994790	Cardiac glycosides induced toxicity in human cells expressing α1-, α2-, or α3-isoforms of Na-K-ATPase Garty, H, Cherniavsky Lev, M, Karlish, SJ	Am. J. Physiol., Cell Physiol.	2015
20388710	Selectivity of digitalis glycosides for isoforms of human Na,K-ATPase Karlish, SJ, Bab-Dinitz, E, Tal, DM, Katz, A, Kapri-Pardes, E, Lifshitz, Y, Goldshleger, R	J. Biol. Chem.	2010