ArticleAmerican journal of physiology. Renal physiology2011
Ouabain activates the Na-K-ATPase signalosome to induce autosomal dominant polycystic kidney disease cell proliferation.
Article in American journal of physiology. Renal physiology, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers.
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Who cites it
30 citing papers in PubMed, 39 citations in OpenAlex.
- Na,K-ATPase mediated and cardiotonic induced signaling in health and disease.Frontiers in physiology · 2025Review
- The cystogenic effects of ouabain in autosomal dominant polycystic kidney disease require cell caveolae.Experimental cell research · 2025Article
- Cardenolide glycosides sensitize gefitinib-induced apoptosis in non-small cell lung cancer: inhibition of NaNaunyn-Schmiedeberg's archives of pharmacology · 2024Article
- Ouabain enhances renal cyst growth in a slowly progressive mouse model of autosomal dominant polycystic kidney disease.American journal of physiology. Renal physiology · 2023Article
- Live cell screening identifies glycosides as enhancers of cardiomyocyte cell cycle activity.Frontiers in cardiovascular medicine · 2022Article
- NaMolecules (Basel, Switzerland) · 2021Review
- Disturbed Presynaptic CaiScience · 2020Article
- Stress Signal Regulation by Na/K-ATPase As a New Approach to Promote Physiological Revascularization in a Mouse Model of Ischemic Retinopathy.Investigative ophthalmology & visual science · 2020Article
- Natural cardenolides suppress coronaviral replication by downregulating JAK1 via a NaBiochemical pharmacology · 2020Article
- 21-Benzylidene digoxin decreases proliferation by inhibiting the EGFR/ERK signaling pathway and induces apoptosis in HeLa cells.Steroids · 2020Article
- Ouabain potentiates the antimicrobial activity of aminoglycosides against Staphylococcus aureus.BMC complementary and alternative medicine · 2019Article
- The cardenolide ouabain suppresses coronaviral replication via augmenting a NaToxicology and applied pharmacology · 2018Article
- Telocinobufagin and Marinobufagin Produce Different Effects in LLC-PK1 Cells: A Case of Functional Selectivity of Bufadienolides.International journal of molecular sciences · 2018Article
- Bufalin induced apoptosis of bladder carcinoma cells through the inactivation of Na+K+-ATPase.Oncology letters · 2018Article
- The Na/K-ATPase Oxidant Amplification Loop Regulates Aging.Scientific reports · 2018Article
- The pump, the exchanger, and the holy spirit: origins and 40-year evolution of ideas about the ouabain-NaAmerican journal of physiology. Cell physiology · 2018Review
- Ouabain-induced apoptosis and inhibition of viability of tubulointerstitial cells by regulating NKA/pSrc/pERK/pAkt/pS6k/caspase 3 may contribute to lupus nephritis development.International journal of clinical and experimental pathology · 2018Article
- Ouabain promotes partial epithelial to mesenchymal transition (EMT) changes in human autosomal dominant polycystic kidney disease (ADPKD) cells.Experimental cell research · 2017Article
- Protein Interaction and Na/K-ATPase-Mediated Signal Transduction.Molecules (Basel, Switzerland) · 2017Review
- On the Many Actions of Ouabain: Pro-Cystogenic Effects in Autosomal Dominant Polycystic Kidney Disease.Molecules (Basel, Switzerland) · 2017Review
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Authors and funding
7 authors at 3 institutions in 2 countries.
Funding
Abstract
The Na-K-ATPase is part of a cell signaling complex, the Na-K-ATPase signalosome, which upon activation by the hormone ouabain regulates the function of different cell types. We previously showed that ouabain induces proliferation of epithelial cells derived from renal cysts of patients with autosomal dominant polycystic kidney disease (ADPKD cells). Here, we investigated the signaling pathways responsible for mediating the effects of ouabain in these cells. Incubation of ADPKD cells with ouabain, in concentrations similar to those found in blood, stimulated phosphorylation of the epidermal growth factor receptor (EGFR) and promoted its association to the Na-K-ATPase. In addition, ouabain activated the kinase Src, but not the related kinase Fyn. Tyrphostin AG1478 and PP2, inhibitors of EGFR and Src, respectively, blocked ouabain-dependent ADPKD cell proliferation. Treatment of ADPKD cells with ouabain also caused phosphorylation of the caveolar protein caveolin-1, and disruption of cell caveolae with methyl-β-cyclodextrin prevented Na-K-ATPase-EGFR interaction and ouabain-induced proliferation of the cells. Downstream effects of ouabain in ADPKD cells included activation of B-Raf and MEK and phosphorylation of the extracellular regulated kinase ERK, which translocated into the ADPKD cell nuclei. Finally, ouabain reduced expression of the cyclin-dependent kinase inhibitors p21 and p27, which are suppressors of cell proliferation. Different from ADPKD cells, ouabain showed no significant effect on B-Raf, p21, and p27 in normal human kidney epithelial cells. Altogether, these results identify intracellular pathways of ouabain-dependent Na-K-ATPase-mediated signaling in ADPKD cells, including EGFR-Src-B-Raf-MEK/ERK, and establish novel mechanisms involved in ADPKD cell proliferation.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.