ATP1A1 binds cardiac glycosides

Stable Identifier
R-HSA-9684068
Type
Reaction [binding]
Species
Homo sapiens
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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.

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
28645727 Inhibition of Non Canonical HIV-1 Tat Secretion Through the Cellular Na+,K+-ATPase Blocks HIV-1 Infection

Agostini, S, Ali, H, Vardabasso, C, Fittipaldi, A, Tasciotti, E, Cereseto, A, Bugatti, A, Rusnati, M, Lusic, M, Giacca, M

EBioMedicine 2017
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