ArticlePflugers Archiv : European journal of physiology2004
Na+/K+ pump and endothelial cell survival: [Na+]i/[K+]i-independent necrosis triggered by ouabain, and protection against apoptosis mediated by elevation of [Na+]i.
Article in Pflugers Archiv : European journal of physiology, 2004. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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Who cites it
18 citing papers in PubMed, 59 citations in OpenAlex.
- Minimalistic transcriptomic signatures permit accurate early prediction of COVID-19 mortality.JCI insight · 2025Article
- Depth of the Steroid Core Location Determines the Mode of Na,K-ATPase Inhibition by Cardiotonic Steroids.International journal of molecular sciences · 2021Article
- Ouabain-Induced Cell Death and Survival. Role of α1-Na,K-ATPase-Mediated Signaling and [NaFrontiers in physiology · 2020Review
- Telocinobufagin and Marinobufagin Produce Different Effects in LLC-PK1 Cells: A Case of Functional Selectivity of Bufadienolides.International journal of molecular sciences · 2018Article
- The Na/K-ATPase Signaling: From Specific Ligands to General Reactive Oxygen Species.International journal of molecular sciences · 2018Review
- Na⁺Molecules (Basel, Switzerland) · 2017Review
- Time- and dose dependent actions of cardiotonic steroids on transcriptome and intracellular content of NaScientific reports · 2017Article
- Ouabain Enhances ADPKD Cell Apoptosis via the Intrinsic Pathway.Frontiers in physiology · 2016Article
- Critical role of the α1-Na(+), K(+)-ATPase subunit in insensitivity of rodent cells to cytotoxic action of ouabain.Apoptosis : an international journal on programmed cell death · 2015Article
- Signaling function of Na,K-ATPase induced by ouabain against LPS as an inflammation model in hippocampus.Journal of neuroinflammation · 2014Article
- Transient receptor potential melastatin 4 and cell death.Pflugers Archiv : European journal of physiology · 2012Review
- The death of ouabain-treated renal epithelial C11-MDCK cells is not mediated by swelling-induced plasma membrane rupture.The Journal of membrane biology · 2011Article
- Ouabain-induced perturbations in intracellular ionic homeostasis regulate death receptor-mediated apoptosis.Apoptosis : an international journal on programmed cell death · 2010Article
- Endogenous cardiotonic steroids: physiology, pharmacology, and novel therapeutic targets.Pharmacological reviews · 2009Review
- Potassium channels in the regulation of pulmonary artery smooth muscle cell proliferation and apoptosis: pharmacotherapeutic implications.British journal of pharmacology · 2008Review
- [Na+]i/[K+]i -independent death of ouabain-treated renal epithelial cells is not mediated by Na+,K+ -ATPase internalization and de novo gene expression.Pflugers Archiv : European journal of physiology · 2008Article
- Intracellular monovalent ions as second messengers.The Journal of membrane biology · 2006Review
- Modest intracellular acidification suppresses death signaling in ouabain-treated cells.Pflugers Archiv : European journal of physiology · 2006Article
Corrections and comments
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Authors and funding
8 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Recent studies have demonstrated the tissue-specific effect of Na+/K+ pump inhibition by ouabain and other cardiac glycosides on cell viability. The vascular endothelium is an initial target of cardiac glycosides employed for the management of congestive heart failure as well as circulating endogenous ouabain-like substances (EOLS), the production of which is augmented in volume-expanded hypertension. This study examined the role of the Na+/K+ pump in the survival of cultured porcine aortic endothelial cells (PAEC). Complete Na+/K+ pump inhibition with ouabain led to PAEC death, indicated by cell detachment and decreased staining with 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT). Based on cell swelling and resistance to benzyloxycarbonyl-Val-Ala-Asp-fluoromethylketone (z-VAD.fmk) a pan-caspase inhibitor, this type of cell death was classified as necrosis. In contrast to ouabain, Na+/K+ pump inhibition in K+-free medium did not affect PAEC viability and sharply attenuated apoptosis triggered by 3H decay-induced DNA damage. Necrosis evoked by ouabain was preserved after dissipation of the transmembrane gradient of K+ and Na+, whereas dissipation of the Na+ gradient abolished the antiapoptotic action of K+-free medium. Comparative analysis of these results and modulation of intracellular Na+ and K+ content by the above-listed stimuli showed that interaction of ouabain with Na+/K+-ATPase triggered necrosis independently of inhibition of Na+/K+ pump-mediated ion fluxes and inversion of the [Na+]i/[K+]i ratio, whereas protection against apoptosis under Na+/K+ pump inhibition in K+-depleted medium was mediated by [Na+]i elevation. The role of Na+/K+ pump-mediated regulation of endothelial cell survival and vascular remodelling seen in hypertension should be investigated further in context of EOLS and chronic treatment with digitalis.
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