Ouabain and Marinobufagenin: Physiological Effects on Human Epithelial and Endothelial Cells

Климанова, Е. А.; Fedorov, Dmitry; Sidorenko, S. V.; Abramicheva, P A; Лопина, О.Д.; Orlov, Sergei N.

doi:10.1134/s0006297920040112

Cited by 5 publications

(1 citation statement)

References 44 publications

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“…Ouabain in concentrations that completely inhibit the transport function of NKA (100 nM-10 µM) triggered the death of various cells with α1S-NKA [32][33][34][35][36][37][38][39][40][41][42][43][44][45][46][47][48][49]. In contrast, treatment of rodent cells containing α1R-NKA with ouabain (1-3 mM), which inhibits the transport function of the enzyme, did not affect the survival [45,[50][51][52][53].…”

Section: Introductionmentioning

confidence: 99%

Depth of the Steroid Core Location Determines the Mode of Na,K-ATPase Inhibition by Cardiotonic Steroids

Tverskoi

Poluektov

Климанова

et al. 2021

IJMS

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Cardiotonic steroids (CTSs) are specific inhibitors of Na,K-ATPase (NKA). They induce diverse physiological effects and were investigated as potential drugs in heart diseases, hypertension, neuroinflammation, antiviral and cancer therapy. Here, we compared the inhibition mode and binding of CTSs, such as ouabain, digoxin and marinobufagenin to NKA from pig and rat kidneys, containing CTSs-sensitive (α1S) and -resistant (α1R) α1-subunit, respectively. Marinobufagenin in contrast to ouabain and digoxin interacted with α1S-NKA reversibly, and its binding constant was reduced due to the decrease in the deepening in the CTSs-binding site and a lower number of contacts between the site and the inhibitor. The formation of a hydrogen bond between Arg111 and Asp122 in α1R-NKA induced the reduction in CTSs’ steroid core deepening that led to the reversible inhibition of α1R-NKA by ouabain and digoxin and the absence of marinobufagenin’s effect on α1R-NKA activity. Our results elucidate that the difference in signaling, and cytotoxic effects of CTSs may be due to the distinction in the deepening of CTSs into the binding side that, in turn, is a result of a bent-in inhibitor steroid core (marinobufagenin in α1S-NKA) or the change of the width of CTSs-binding cavity (all CTSs in α1R-NKA).

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