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Ouabain and Marinobufagenin: Physiological Effects on Human Epithelial and Endothelial Cells.
Biochemistry (Mosc). 2020 Apr; 85(4):507-515.B

Abstract

Long-term study on the identification of Na,K-ATPase endogenous inhibitors in mammalian tissues has resulted in the discovery of ouabain, marinobufagenin (MBG), and other cardiotonic steroids (CTS) in the blood plasma. Production of ouabain and MBG is increased in essential hypertension and other diseases associated with hypervolemia. Here, we compared the effects of ouabain and MBG on the Na,K-ATPase activity (measured as the transport of Na+, K+, and Rb+ ions) and proliferation and death of human renal epithelial cells (HRECs) and human umbilical vein endothelial cells (HUVEC) expressing α1-Na,K-ATPase. Ouabain concentration that provided the half-maximal inhibition of the Rb+ influx (IC50) into HRECs and HUVECs was 0.07 μM. In both types of cells, the IC50 values for MBG were 10 times higher than for ouabain. Incubation of HREC and HUVEC with 0.001-0.01 μM ouabain for 30 h resulted in 40% increase in the [3H]thymidine incorporation into DNA; further elevation of ouabain concentration to 0.1 μM completely suppressed DNA synthesis. MBG at the concentration of 0.1 μM activated DNA synthesis by 25% in HRECs, but not in HUVECs; 1 μM MBG completely inhibited DNA synthesis in HRECs and by 50% in HUVECs. In contrast to HRECs, incubation of HUVECs in the serum-free medium induced apoptosis, which was almost completely suppressed by ouabain and MBG at the concentrations of 0.1 and 3 μM, respectively. Based on these data, we can conclude that (i) the effect of MBG at the concentrations detected in the blood plasma (<0.01 μM) on HRECs and HUVECs was not due to the changes in the [Na+]i/[K+]i ratio; (ii) the effect of physiological concentrations of ouabain on these cells might be mediated by the activation of Na,K-ATPase, leading to cell proliferation.

Authors+Show Affiliations

Lomonosov Moscow State University, Faculty of Biology, Moscow, 119234, Russia. klimanova.ea@yandex.ru.Lomonosov Moscow State University, Faculty of Biology, Moscow, 119234, Russia.Lomonosov Moscow State University, Faculty of Biology, Moscow, 119234, Russia.Lomonosov Moscow State University, Faculty of Biology, Moscow, 119234, Russia.Lomonosov Moscow State University, Faculty of Biology, Moscow, 119234, Russia.Lomonosov Moscow State University, Faculty of Biology, Moscow, 119234, Russia.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

32569558

Citation

Klimanova, E A., et al. "Ouabain and Marinobufagenin: Physiological Effects On Human Epithelial and Endothelial Cells." Biochemistry. Biokhimiia, vol. 85, no. 4, 2020, pp. 507-515.
Klimanova EA, Fedorov DA, Sidorenko SV, et al. Ouabain and Marinobufagenin: Physiological Effects on Human Epithelial and Endothelial Cells. Biochemistry Mosc. 2020;85(4):507-515.
Klimanova, E. A., Fedorov, D. A., Sidorenko, S. V., Abramicheva, P. A., Lopina, O. D., & Orlov, S. N. (2020). Ouabain and Marinobufagenin: Physiological Effects on Human Epithelial and Endothelial Cells. Biochemistry. Biokhimiia, 85(4), 507-515. https://doi.org/10.1134/S0006297920040112
Klimanova EA, et al. Ouabain and Marinobufagenin: Physiological Effects On Human Epithelial and Endothelial Cells. Biochemistry Mosc. 2020;85(4):507-515. PubMed PMID: 32569558.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Ouabain and Marinobufagenin: Physiological Effects on Human Epithelial and Endothelial Cells. AU - Klimanova,E A, AU - Fedorov,D A, AU - Sidorenko,S V, AU - Abramicheva,P A, AU - Lopina,O D, AU - Orlov,S N, PY - 2020/6/23/entrez PY - 2020/6/23/pubmed PY - 2020/6/23/medline SP - 507 EP - 515 JF - Biochemistry. Biokhimiia JO - Biochemistry Mosc. VL - 85 IS - 4 N2 - Long-term study on the identification of Na,K-ATPase endogenous inhibitors in mammalian tissues has resulted in the discovery of ouabain, marinobufagenin (MBG), and other cardiotonic steroids (CTS) in the blood plasma. Production of ouabain and MBG is increased in essential hypertension and other diseases associated with hypervolemia. Here, we compared the effects of ouabain and MBG on the Na,K-ATPase activity (measured as the transport of Na+, K+, and Rb+ ions) and proliferation and death of human renal epithelial cells (HRECs) and human umbilical vein endothelial cells (HUVEC) expressing α1-Na,K-ATPase. Ouabain concentration that provided the half-maximal inhibition of the Rb+ influx (IC50) into HRECs and HUVECs was 0.07 μM. In both types of cells, the IC50 values for MBG were 10 times higher than for ouabain. Incubation of HREC and HUVEC with 0.001-0.01 μM ouabain for 30 h resulted in 40% increase in the [3H]thymidine incorporation into DNA; further elevation of ouabain concentration to 0.1 μM completely suppressed DNA synthesis. MBG at the concentration of 0.1 μM activated DNA synthesis by 25% in HRECs, but not in HUVECs; 1 μM MBG completely inhibited DNA synthesis in HRECs and by 50% in HUVECs. In contrast to HRECs, incubation of HUVECs in the serum-free medium induced apoptosis, which was almost completely suppressed by ouabain and MBG at the concentrations of 0.1 and 3 μM, respectively. Based on these data, we can conclude that (i) the effect of MBG at the concentrations detected in the blood plasma (<0.01 μM) on HRECs and HUVECs was not due to the changes in the [Na+]i/[K+]i ratio; (ii) the effect of physiological concentrations of ouabain on these cells might be mediated by the activation of Na,K-ATPase, leading to cell proliferation. SN - 1608-3040 UR - https://www.unboundmedicine.com/medline/citation/32569558/Ouabain_and_Marinobufagenin:_Physiological_Effects_on_Human_Epithelial_and_Endothelial_Cells L2 - https://dx.doi.org/10.1134/S0006297920040112 DB - PRIME DP - Unbound Medicine ER -
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