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Biochemistry (Moscow)

, Volume 81, Issue 8, pp 876–883 | Cite as

Effects of ouabain on proliferation of human endothelial cells correlate with Na+,K+-ATPase activity and intracellular ratio of Na+ and K+

  • A. M. Tverskoi
  • S. V. Sidorenko
  • E. A. Klimanova
  • O. A. Akimova
  • L. V. Smolyaninova
  • O. D. Lopina
  • S. N. OrlovEmail author
Article

Abstract

Side-by-side with inhibition of the Na+,K+-ATPase ouabain and other cardiotonic steroids (CTS) can affect cell functions by mechanisms other than regulation of the intracellular Na+ and K+ ratio ([Na+]i/[K+]i). Thus, we compared the doseand time-dependences of the effect of ouabain on intracellular [Na+]i/[K+]i ratio, Na+,K+-ATPase activity, and proliferation of human umbilical vein endothelial cells (HUVEC). Treatment of the cells with 1-3 nM ouabain for 24-72 h decreased the [Na+]i/[K+]i ratio and increased cell proliferation by 20-50%. We discovered that the same ouabain concentrations increased Na+,K+-ATPase activity by 25-30%, as measured by the rate of 86Rb+ influx. Higher ouabain concentrations inhibited Na+,K+-ATPase, increased [Na+]i/[K+]i ratio, suppressed cell growth, and caused cell death. When cells were treated with low ouabain concentrations for 48 or 72 h, a negative correlation between [Na+]i/[K+]i ratio and cell growth activation was observed. In cells treated with high ouabain concentrations for 24 h, the [Na+]i/[K+]i ratio correlated positively with proliferation inhibition. These data demonstrate that inhibition of HUVEC proliferation at high CTS concentrations correlates with dissipation of the Na+ and K+ concentration gradients, whereas cell growth stimulation by low CTS doses results from activation of Na+,K+-ATPase and decrease in the [Na+]i/[K+]i ratio.

Keywords

proliferation endothelium Na+,K+-ATPase ouabain intracellular Na+ and K+ 

Abbreviations

CTS

cardiotonic steroids

HUVEC

human umbilical vein endothelial cells

IEG

immediate early genes

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Copyright information

© Pleiades Publishing, Ltd. 2016

Authors and Affiliations

  • A. M. Tverskoi
    • 1
  • S. V. Sidorenko
    • 1
  • E. A. Klimanova
    • 1
  • O. A. Akimova
    • 1
  • L. V. Smolyaninova
    • 1
  • O. D. Lopina
    • 1
  • S. N. Orlov
    • 1
    • 2
    • 3
    Email author
  1. 1.Faculty of BiologyLomonosov Moscow State UniversityMoscowRussia
  2. 2.Tomsk National Research State UniversityTomskRussia
  3. 3.Siberian State Medical UniversityTomskRussia

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