title: Oxidative regulation of the Na(+)-K(+) pump in the cardiovascular system.
abstract: The Na(+)-K(+) pump is an essential heterodimeric membrane protein, which maintains electrochemical gradients for Na(+) and K(+) across cell membranes in all tissues. We have identified glutathionylation, a reversible posttranslational redox modification, of the Na(+)-K(+) pump's β1 subunit as a regulatory mechanism of pump activity. Oxidative inhibition of the Na(+)-K(+) pump by angiotensin II- and β1-adrenergic receptor-coupled signaling via NADPH oxidase activation demonstrates the relevance of this regulatory mechanism in cardiovascular physiology and pathophysiology. This has implications for dysregulation of intracellular Na(+) and Ca(2+) as well as increased oxidative stress in heart failure, myocardial ischemia-reperfusion, and regulation of vascular tone under conditions of elevated oxidative stress. Treatment strategies that are able to reverse this oxidative inhibition of the Na(+)-K(+) pump have the potential for cardiovascular-protective effects.
authors.affiliation: North Shore Heart Research Group, Kolling Institute of Medical Research, University of Sydney, St Leonards, NSW 2065, Australia; Department of Cardiology, Royal North Shore Hospital, Sydney, NSW, Australia. Electronic address: gfigtree@med.usyd.edu.au.
authors.forename: Gemma A
authors.initials: GA
authors.lastname: Figtree
authors.affiliation: North Shore Heart Research Group, Kolling Institute of Medical Research, University of Sydney, St Leonards, NSW 2065, Australia; Department of Cardiology, Royal North Shore Hospital, Sydney, NSW, Australia.
authors.forename: Galougahi
authors.initials: G
authors.lastname: Keyvan Karimi
authors.affiliation: North Shore Heart Research Group, Kolling Institute of Medical Research, University of Sydney, St Leonards, NSW 2065, Australia.
authors.forename: Chia-Chi
authors.initials: CC
authors.lastname: Liu
authors.affiliation: North Shore Heart Research Group, Kolling Institute of Medical Research, University of Sydney, St Leonards, NSW 2065, Australia; Department of Cardiology, Royal North Shore Hospital, Sydney, NSW, Australia.
authors.forename: Helge H
authors.initials: HH
authors.lastname: Rasmussen
mesh_terms: D000818:Animals; D002319:Cardiovascular System / Q000201:enzymology*; D005978:Glutathione / Q000378:metabolism*; D006333:Heart Failure / Q000201:enzymology*; D006801:Humans; D015428:Myocardial Reperfusion Injury / Q000201:enzymology; D010084:Oxidation-Reduction; D018384:Oxidative Stress; D010766:Phosphorylation; D011487:Protein Conformation; D011499:Protein Processing, Post-Translational; D000254:Sodium-Potassium-Exchanging ATPase / Q000737:chemistry / Q000378:metabolism*
chemical_list: D000254:Sodium-Potassium-Exchanging ATPase; D005978:Glutathione
keywords: Free radicals; Glutaredoxin; Glutathionylation; NADPH oxidase; Na(+)–K(+) pump