Stimulation of the cardiac myocyte Na<sup>+</sup>-K<sup>+</sup> pump due to reversal of its constitutive oxidative inhibition

Chia, Karin K. M., Liu, Chia-Chi, Hamilton, Elisha J., Garcia, Alvaro, Fry, Natasha A., Hannam, William, Figtree, Gemma A. and Rasmussen, Helge H. (2015) Stimulation of the cardiac myocyte Na<sup>+</sup>-K<sup>+</sup> pump due to reversal of its constitutive oxidative inhibition. American Journal of Physiology - Cell Physiology, 309 4: C239-C250. doi:10.1152/ajpcell.00392.2014


Author Chia, Karin K. M.
Liu, Chia-Chi
Hamilton, Elisha J.
Garcia, Alvaro
Fry, Natasha A.
Hannam, William
Figtree, Gemma A.
Rasmussen, Helge H.
Title Stimulation of the cardiac myocyte Na+-K+ pump due to reversal of its constitutive oxidative inhibition
Journal name American Journal of Physiology - Cell Physiology   Check publisher's open access policy
ISSN 1522-1563
Publication date 2015-08-18
Sub-type Article (original research)
DOI 10.1152/ajpcell.00392.2014
Open Access Status Not Open Access
Volume 309
Issue 4
Start page C239
End page C250
Total pages 12
Place of publication Bethesda, MD, United States
Publisher American Physiological Society
Collection year 2016
Language eng
Formatted abstract
Protein kinase C can activate NADPH oxidase and induce glutathionylation of the β1-Na+-K+ pump subunit, inhibiting activity of the catalytic α-subunit. To examine if signaling of nitric oxide-induced soluble guanylyl cyclase (sGC)/cGMP/protein kinase G can cause Na+-K+ pump stimulation by counteracting PKC/NADPH oxidase-dependent inhibition, cardiac myocytes were exposed to ANG II to activate NADPH oxidase and inhibit Na+-K+ pump current (Ip). Coexposure to 3-(5′-hydroxymethyl-2′-furyl)-1-benzylindazole (YC-1) to stimulate sGC prevented the decrease of Ip. Prevention of the decrease was abolished by inhibition of protein phosphatases (PP) 2A but not by inhibition of PP1, and it was reproduced by an activator of PP2A. Consistent with a reciprocal relationship between β1-Na+-K+ pump subunit glutathionylation and pump activity, YC-1 decreased ANG II-induced β1-subunit glutathionylation. The decrease induced by YC-1 was abolished by a PP2A inhibitor. YC-1 decreased phosphorylation of the cytosolic p47phox NADPH oxidase subunit and its coimmunoprecipitation with the membranous p22phox subunit, and it decreased O2·−-sensitive dihydroethidium fluorescence of myocytes. Addition of recombinant PP2A to myocyte lysate decreased phosphorylation of p47phox indicating the subunit could be a substrate for PP2A. The effects of YC-1 to decrease coimmunoprecipitation of p22phox and p47phox NADPH oxidase subunits and decrease β1-Na+-K+ pump subunit glutathionylation were reproduced by activation of nitric oxide-dependent receptor signaling. We conclude that sGC activation in cardiac myocytes causes a PP2A-dependent decrease in NADPH oxidase activity and a decrease in β1 pump subunit glutathionylation. This could account for pump stimulation with neurohormonal oxidative stress expected in vivo.
Keyword Glutathionylation
Nitric oxide
Oxidative stress
Sodium-potassium (Na+-K+)-ATPase
Soluble guanylyl cyclase
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: Official 2016 Collection
School of Medicine Publications
 
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