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

• Published in: Biochemistry (Moscow) Vol. 81; no. 8; pp. 876 - 883
• Main Authors: Tverskoi, A. M., Sidorenko, S. V., Klimanova, E. A., Akimova, O. A., Smolyaninova, L. V., Lopina, O. D., Orlov, S. N.
• Format: Journal Article
• Language: English
• Published: Moscow Pleiades Publishing 01.08.2016
• Subjects: Biochemistry; Biomedical and Life Sciences; Biomedicine; Bioorganic Chemistry; Cell Death - drug effects; Cell Proliferation - drug effects; Dose-Response Relationship, Drug; Human Umbilical Vein Endothelial Cells - cytology; Human Umbilical Vein Endothelial Cells - metabolism; Humans; Ion Transport - drug effects; Life Sciences; Microbiology; Ouabain - pharmacology; Potassium - metabolism; Sodium - metabolism; Sodium-Potassium-Exchanging ATPase - metabolism; ouabain; intracellular Na; endothelium; Na; proliferation; ATPase; and K; K
• ISSN: 0006-2979; 1608-3040
• DOI: 10.1134/S0006297916080083

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 86 Rb + 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.