Reversible oxidative modification: implications for cardiovascular physiology and pathophysiology.
Reminiscent of phosphorylation, cellular signaling can induce reversible forms of oxidative modification of proteins with an impact on their function. Redox signaling can be coupled to cell membrane receptors for hormones and be a physiologic means of regulating protein function, whereas pathologic increases in oxidative stress may induce disease processes. Here we review the role of reversible oxidative modification of proteins in the regulation of their function with particular emphasis on the cardiac Na(+)-K(+) pump. We describe how protein-kinase-dependent activation of redox signaling, mediated by angiotensin receptors and β adrenergic receptors, induces glutathionylation of an identified cysteine residue in the β(1) subunit of the α/β pump heterodimer; and we discuss how this may link neurohormonal abnormalities, increased oxidative stress, and cardiac myocyte Na(+) dysregulation and heart failure with important implications for treatment.
North Shore Heart Research Group, Kolling Institute, University of Sydney, NSW 2006, Australia. helge.rasmussen@sydney.edu.au
Helge H
HH
Rasmussen
Elisha J
EJ
Hamilton
Chia-Chi
CC
Liu
Gemma A
GA
Figtree
D000818:Animals; D005978:Glutathione / Q000378:metabolism; D006331:Heart Diseases / Q000201:enzymology* / Q000503:physiopathology; D006801:Humans; D009206:Myocardium / Q000201:enzymology*; D010084:Oxidation-Reduction; D018384:Oxidative Stress; D011494:Protein Kinases / Q000378:metabolism; D011499:Protein Processing, Post-Translational; D011943:Receptors, Adrenergic, beta / Q000378:metabolism; D011945:Receptors, Angiotensin / Q000378:metabolism; D015398:Signal Transduction; D000254:Sodium-Potassium-Exchanging ATPase / Q000378:metabolism*
D011943:Receptors, Adrenergic, beta; D011945:Receptors, Angiotensin; D011494:Protein Kinases; D000254:Sodium-Potassium-Exchanging ATPase; D005978:Glutathione