ArticleThe Journal of biological chemistry2010
Activation of cAMP-dependent signaling induces oxidative modification of the cardiac Na+-K+ pump and inhibits its activity.
Article in The Journal of biological chemistry, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.
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Who cites it
27 citing papers in PubMed.
- Post-translational modifications of na+/K+-atpase subunits: regulatory mechanisms and functional implications.Frontiers in cell and developmental biology · 2026Review
- Pericardial Adipose Tissue-Derived Leptin Promotes Myocardial Apoptosis in High-Fat Diet-Induced Obese Rats Through Janus Kinase 2/Reactive Oxygen Species/Na+/K+-ATPase Signaling Pathway.Journal of the American Heart Association · 2021Article
- FXYD proteins and sodium pump regulatory mechanisms.The Journal of general physiology · 2021Review
- Physiological Effects of the Electrogenic Current Generated by the NaBioelectricity · 2020Article
- Control of cardiac contraction by sodium: Promises, reckonings, and new beginnings.Cell calcium · 2020Review
- Article
- Short-Term Exposure to High Sucrose Levels near Weaning Has a Similar Long-Lasting Effect on Hypertension as a Long-Term Exposure in Rats.Nutrients · 2018Article
- Noradrenergic β-Adrenoceptor-Mediated Intracellular Molecular Mechanism of Na-K ATPase Subunit Expression in C6 Cells.Cellular and molecular neurobiology · 2018Article
- Protein Interaction and Na/K-ATPase-Mediated Signal Transduction.Molecules (Basel, Switzerland) · 2017Review
- Protein Thiol Redox Signaling in Monocytes and Macrophages.Antioxidants & redox signaling · 2016Review
- "Oxygen Sensing" by Na,K-ATPase: These Miraculous Thiols.Frontiers in physiology · 2016Review
- cAMP induction by ouabain promotes endothelin-1 secretion via MAPK/ERK signaling in beating rabbit atria.The Korean journal of physiology & pharmacology : official journal of the Korean Physiological Society and the Korean Society of Pharmacology · 2016Article
- β3-Adrenoceptor activation relieves oxidative inhibition of the cardiac Na+-K+ pump in hyperglycemia induced by insulin receptor blockade.American journal of physiology. Cell physiology · 2015Article
- Stimulation of the cardiac myocyte Na+-K+ pump due to reversal of its constitutive oxidative inhibition.American journal of physiology. Cell physiology · 2015Article
- The effect of exercise and beta2-adrenergic stimulation on glutathionylation and function of the Na,K-ATPase in human skeletal muscle.Physiological reports · 2015Article
- β2-adrenergic stimulation enhances Ca2+ release and contractile properties of skeletal muscles, and counteracts exercise-induced reductions in Na+-K+-ATPase Vmax in trained men.The Journal of physiology · 2014Article
- Analysis of oxidative stress enzymes and structural and functional proteins on human aortic tissue from different aortopathies.Oxidative medicine and cellular longevity · 2014Article
- Oxidative inhibition of the vascular Na+-K+ pump via NADPH oxidase-dependent β1-subunit glutathionylation: implications for angiotensin II-induced vascular dysfunction.Free radical biology & medicine · 2013Article
- Protein kinase-dependent oxidative regulation of the cardiac Na+-K+ pump: evidence from in vivo and in vitro modulation of cell signalling.The Journal of physiology · 2013Article
- Regulation of the cardiac sodium pump.Cellular and molecular life sciences : CMLS · 2013Review
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Authors and funding
7 authors.
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Abstract
Cellular signaling can inhibit the membrane Na(+)-K(+) pump via protein kinase C (PKC)-dependent activation of NADPH oxidase and a downstream oxidative modification, glutathionylation, of the beta(1) subunit of the pump alpha/beta heterodimer. It is firmly established that cAMP-dependent signaling also regulates the pump, and we have now examined the hypothesis that such regulation can be mediated by glutathionylation. Exposure of rabbit cardiac myocytes to the adenylyl cyclase activator forskolin increased the co-immunoprecipitation of NADPH oxidase subunits p47(phox) and p22(phox), required for its activation, and increased superoxide-sensitive fluorescence. Forskolin also increased glutathionylation of the Na(+)-K(+) pump beta(1) subunit and decreased its co-immunoprecipitation with the alpha(1) subunit, findings similar to those already established for PKC-dependent signaling. The decrease in co-immunoprecipitation indicates a decrease in the alpha(1)/beta(1) subunit interaction known to be critical for pump function. In agreement with this, forskolin decreased ouabain-sensitive electrogenic Na(+)-K(+) pump current (arising from the 3:2 Na(+):K(+) exchange ratio) of voltage-clamped, internally perfused myocytes. The decrease was abolished by the inclusion of superoxide dismutase, the inhibitory peptide for the epsilon-isoform of PKC or inhibitory peptide for NADPH oxidase in patch pipette solutions that perfuse the intracellular compartment. Pump inhibition was also abolished by inhibitors of protein kinase A and phospholipase C. We conclude that cAMP- and PKC-dependent inhibition of the cardiac Na(+)-K(+) pump occurs via a shared downstream oxidative signaling pathway involving NADPH oxidase activation and glutathionylation of the pump beta(1) subunit.
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