ArticleApoptosis : an international journal on programmed cell death2015
Critical role of the α1-Na(+), K(+)-ATPase subunit in insensitivity of rodent cells to cytotoxic action of ouabain.
Article in Apoptosis : an international journal on programmed cell death, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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Who cites it
17 citing papers in PubMed, 39 citations in OpenAlex.
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- Overexpression of ATP1B2 promotes cancer cell migration and inhibits apoptosis in patients with esophageal squamous cell carcinoma.Oncology reports · 2025Article
- Mechanisms mediating effects of cardiotonic steroids in mammalian blood cells.Frontiers in pharmacology · 2025Review
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- Depth of the Steroid Core Location Determines the Mode of Na,K-ATPase Inhibition by Cardiotonic Steroids.International journal of molecular sciences · 2021Article
- The NaCellular and molecular life sciences : CMLS · 2021Review
- Na,K-ATPase as a target for endogenous cardiotonic steroids: What's the evidence?Genes & diseases · 2021Review
- Ouabain-Induced Gene Expression Changes in Human iPSC-Derived Neuron Culture Expressing Dopamine and cAMP-Regulated Phosphoprotein 32 and GABA Receptors.Brain sciences · 2021Article
- Steroid Glycosides Hyrcanoside and Deglucohyrcanoside: On Isolation, Structural Identification, and Anticancer Activity.Foods (Basel, Switzerland) · 2021Article
- Ouabain-Induced Cell Death and Survival. Role of α1-Na,K-ATPase-Mediated Signaling and [NaFrontiers in physiology · 2020Review
- Cardiac glycosides decrease influenza virus replication by inhibiting cell protein translational machinery.American journal of physiology. Lung cellular and molecular physiology · 2019Article
- Transcriptomic changes triggered by ouabain in rat cerebellum granule cells: Role of α3- and α1-Na+,K+-ATPase-mediated signaling.PloS one · 2019Article
- Oleandrin synergizes with cisplatin in human osteosarcoma cells by enhancing cell apoptosis through activation of the p38 MAPK signaling pathway.Cancer chemotherapy and pharmacology · 2018Article
- Na⁺Molecules (Basel, Switzerland) · 2017Review
- Time- and dose dependent actions of cardiotonic steroids on transcriptome and intracellular content of NaScientific reports · 2017Article
- Skeletal muscle as an endocrine organ: Role of [NaGenes & diseases · 2015Article
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Authors and funding
8 authors at 4 institutions in 2 countries.
Funding
Abstract
In rodents, ubiquitous α1-Na(+), K(+)-ATPase is inhibited by ouabain and other cardiotonic steroids (CTS) at ~10(3)-fold higher concentrations than those effective in other mammals. To examine the specific roles of the CTS-sensitive α1S- and CTS-resistant α1R-Na(+), K(+)-ATPase isoforms, we compared the effects of ouabain on intracellular Na(+) and K(+) content, cell survival, and mitogen-activated protein kinases (MAPK) in human and rat vascular smooth muscle cells (HASMC and RASMC), human and rat endothelial cells (HUVEC and RAEC), and human and rat brain astrocytes. 6-h exposure of HASMC and HUVEC to 3 μM ouabain dramatically increased the intracellular [Na(+)]/[K(+)] ratio to the same extend as in RASMC and RAEC treated with 3000 μM ouabain. In 24, 3 μM ouabain triggered the death of all types of human cells used in this study. Unlike human cells, we did not detect any effect of 3000-5000 μM ouabain on the survival of rat cells, or smooth muscle cells from mouse aorta (MASMC). Unlike in the wild-type α1(R/R) mouse, ouabain triggered death of MASMC from α1(S/S) mouse expressing human α1-Na(+), K(+)-ATPase. Furthermore, transfection of HUVEC with rat α1R-Na(+), K(+)-ATPase protected them from the ouabain-induced death. In HUVEC, ouabain led to phosphorylation of p38 MAPK, whereas in RAEC it stimulated phosphorylation of ERK1/2. Overall, our results, demonstrate that the drastic differences in cytotoxic action of ouabain on human and rodent cells are caused by unique features of α1S/α1R-Na(+), K(+)-ATPase, rather than by any downstream CTS-sensitive/resistant components of the cell death machinery.
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