ArticleThe Journal of biological chemistry2014
Ouabain-induced internalization and lysosomal degradation of the Na+/K+-ATPase.
Article in The Journal of biological chemistry, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.
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Who cites it
25 citing papers in PubMed, 37 citations in OpenAlex.
- Article
- Peptide hormone spexin restores beta cell function and improves glycaemic control in mice via regulation of the sodium-potassium pump.Diabetologia · 2026Article
- Short-Term Simulated High-Altitude Hypoxia Enhances Na,K-ATPase Efficiency in Maintaining Rat Diaphragm Electrogenesis.Bulletin of experimental biology and medicine · 2025Article
- Mechanisms mediating effects of cardiotonic steroids in mammalian blood cells.Frontiers in pharmacology · 2025Review
- Na,K-ATPase mediated and cardiotonic induced signaling in health and disease.Frontiers in physiology · 2025Review
- Cardenolide glycosides sensitize gefitinib-induced apoptosis in non-small cell lung cancer: inhibition of NaNaunyn-Schmiedeberg's archives of pharmacology · 2024Article
- Identified and potential internalization signals involved in trafficking and regulation of NaMolecular and cellular biochemistry · 2024Review
- Bioactive C21 Steroidal Glycosides fromMolecules (Basel, Switzerland) · 2023Article
- The Alpha-1 Subunit of the NaInternational journal of molecular sciences · 2023Article
- Short-Term Mild Hypoxia Modulates Na,K-ATPase to Maintain Membrane Electrogenesis in Rat Skeletal Muscle.International journal of molecular sciences · 2022Article
- Article
- Article
- A High-Throughput Small Molecule Screen Identifies Ouabain as Synergistic with miR-34a in Killing Lung Cancer Cells.iScience · 2020Article
- The alpha-1 subunit of the Na+,K+-ATPase (ATP1A1) is required for macropinocytic entry of respiratory syncytial virus (RSV) in human respiratory epithelial cells.PLoS pathogens · 2019Article
- AMPK alleviates high uric acid-induced NaExperimental & molecular medicine · 2019Article
- Energy handling in renal tubular epithelial cells of the hamster, a native hibernator, under warm anoxia or reoxygenation.Biomedical reports · 2018Article
- Impaired NaExperimental & molecular medicine · 2018Article
- Anticancer and Immunogenic Properties of Cardiac Glycosides.Molecules (Basel, Switzerland) · 2017Review
- Sodium potassium adenosine triphosphatase (Na/K-ATPase) as a therapeutic target for uremic cardiomyopathy.Expert opinion on therapeutic targets · 2017Review
- Membrane lipid rafts are disturbed in the response of rat skeletal muscle to short-term disuse.American journal of physiology. Cell physiology · 2017Article
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Internalization of the Na(+)/K(+)-ATPase (the Na(+) pump) has been studied in the human lung carcinoma cell line H1299 that expresses YFP-tagged α1 from its normal genomic localization. Both real-time imaging and surface biotinylation have demonstrated internalization of α1 induced by ≥100 nm ouabain which occurs in a time scale of hours. Unlike previous studies in other systems, the ouabain-induced internalization was insensitive to Src or PI3K inhibitors. Accumulation of α1 in the cells could be augmented by inhibition of lysosomal degradation but not by proteosomal inhibitors. In agreement, the internalized α1 could be colocalized with the lysosomal marker LAMP1 but not with Golgi or nuclear markers. In principle, internalization could be triggered by a conformational change of the ouabain-bound Na(+)/K(+)-ATPase molecule or more generally by the disruption of cation homeostasis (Na(+), K(+), Ca(2+)) due to the partial inhibition of active Na(+) and K(+) transport. Overexpression of ouabain-insensitive rat α1 failed to inhibit internalization of human α1 expressed in the same cells. In addition, incubating cells in a K(+)-free medium did not induce internalization of the pump or affect the response to ouabain. Thus, internalization is not the result of changes in the cellular cation balance but is likely to be triggered by a conformational change of the protein itself. In physiological conditions, internalization may serve to eliminate pumps that have been blocked by endogenous ouabain or other cardiac glycosides. This mechanism may be required due to the very slow dissociation of the ouabain·Na(+)/K(+)-ATPase complex.
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