ArticleThe Journal of biological chemistry2011
FXYD proteins reverse inhibition of the Na+-K+ pump mediated by glutathionylation of its beta1 subunit.
Article in The Journal of biological chemistry, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 52 papers.
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Who cites it
52 citing papers in PubMed, 92 citations in OpenAlex.
- Oral digoxin effects on exercise performance, KThe Journal of physiology · 2022Trial
- The functions of FXYD family members in human health and disease.Genes & diseases · 2026Review
- Post-translational modifications of na+/K+-atpase subunits: regulatory mechanisms and functional implications.Frontiers in cell and developmental biology · 2026Review
- Cytochrome c and Ouabain Binding Site of Na,K-ATPase.Cell biochemistry and biophysics · 2025Article
- FXYD3 Is Frequently Expressed in Pancreatic Ductal Adenocarcinoma but Does Not Predict Survival.Cancer medicine · 2025Article
- Molecular Basis of Na, K-ATPase Regulation of Diseases: Hormone and FXYD2 Interactions.International journal of molecular sciences · 2024Review
- The effect of cytochrome c on Na,K-ATPase.Journal of bioenergetics and biomembranes · 2024Article
- ATP1A1-linked diseases require a malfunctioning protein product from one allele.Biochimica et biophysica acta. Molecular cell research · 2024Article
- FXYD3 functionally demarcates an ancestral breast cancer stem cell subpopulation with features of drug-tolerant persisters.The Journal of clinical investigation · 2023Article
- Hypoxia and HIF-1α Regulate the Activity and Expression of Na,K-ATPase Subunits in H9c2 Cardiomyoblasts.Current issues in molecular biology · 2023Article
- Hypoxic Stress-Dependent Regulation of Na,K-ATPase in Ischemic Heart Disease.International journal of molecular sciences · 2023Review
- The NaFrontiers in endocrinology · 2023Review
- Effect of HJournal of bioenergetics and biomembranes · 2022Article
- FXYD3 facilitates NaAmerican journal of physiology. Cell physiology · 2022Article
- Displacement of Native FXYD Protein From NaFrontiers in oncology · 2022Article
- FXYD proteins and sodium pump regulatory mechanisms.The Journal of general physiology · 2021Review
- NaMolecules (Basel, Switzerland) · 2021Review
- FXYD protein isoforms differentially modulate human Na/K pump function.The Journal of general physiology · 2020Article
- The Redox-Sensitive Na/K-ATPase Signaling in Uremic Cardiomyopathy.International journal of molecular sciences · 2020Review
- Dysregulation of the glutaredoxin/American journal of physiology. Cell physiology · 2020Article
Corrections and comments
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Authors and funding
10 authors at 5 institutions in 4 countries.
Funding
Abstract
The seven members of the FXYD protein family associate with the Na(+)-K(+) pump and modulate its activity. We investigated whether conserved cysteines in FXYD proteins are susceptible to glutathionylation and whether such reactivity affects Na(+)-K(+) pump function in cardiac myocytes and Xenopus oocytes. Glutathionylation was detected by immunoblotting streptavidin precipitate from biotin-GSH loaded cells or by a GSH antibody. Incubation of myocytes with recombinant FXYD proteins resulted in competitive displacement of native FXYD1. Myocyte and Xenopus oocyte pump currents were measured with whole-cell and two-electrode voltage clamp techniques, respectively. Native FXYD1 in myocytes and FXYD1 expressed in oocytes were susceptible to glutathionylation. Mutagenesis identified the specific cysteine in the cytoplasmic terminal that was reactive. Its reactivity was dependent on flanking basic amino acids. We have reported that Na(+)-K(+) pump β(1) subunit glutathionylation induced by oxidative signals causes pump inhibition in a previous study. In the present study, we found that β(1) subunit glutathionylation and pump inhibition could be reversed by exposing myocytes to exogenous wild-type FXYD3. A cysteine-free FXYD3 derivative had no effect. Similar results were obtained with wild-type and mutant FXYD proteins expressed in oocytes. Glutathionylation of the β(1) subunit was increased in myocardium from FXYD1(-/-) mice. In conclusion, there is a dependence of Na(+)-K(+) pump regulation on reactivity of two specifically identified cysteines on separate components of the multimeric Na(+)-K(+) pump complex. By facilitating deglutathionylation of the β(1) subunit, FXYD proteins reverse oxidative inhibition of the Na(+)-K(+) pump and play a dynamic role in its regulation.
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Registered trials
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.