NAD(P)H oxidase subunit p47^sup phox^ is elevated, and p47^sup phox^ knockout prevents diaphragm contractile dysfunction in heart failure

Patients with chronic heart failure (CHF) have dyspnea and exercise intolerance, which are caused in part by diaphragm abnormalities. Oxidants impair diaphragm contractile function, and CHF increases diaphragm oxidants. However, the specific source of oxidants and its relevance to diaphragm abnormal...

Full description

Saved in:
Bibliographic Details
Published inAmerican journal of physiology. Lung cellular and molecular physiology Vol. 309; no. 5; p. L497
Main Authors Ahn, Bumsoo, Beharry, Adam W, Frye, Gregory S, Judge, Andrew R, Ferreira, Leonardo F
Format Journal Article
LanguageEnglish
Published Bethesda American Physiological Society 01.09.2015
Subjects
Biochemistry
Heart failure
Phosphorylation
Physiology
Respiration
RNA-protein interactions
Online AccessGet full text

Cover

More Information
Summary:Patients with chronic heart failure (CHF) have dyspnea and exercise intolerance, which are caused in part by diaphragm abnormalities. Oxidants impair diaphragm contractile function, and CHF increases diaphragm oxidants. However, the specific source of oxidants and its relevance to diaphragm abnormalities in CHF is unclear. The p47...-dependent Nox2 isoform of NAD(P)H oxidase is a putative source of diaphragm oxidants. Thus, we conducted our study with the goal of determining the effects of CHF on the diaphragm levels of Nox2 complex subunits and test the hypothesis that p47... knockout prevents diaphragm contractile dysfunction elicited by CHF. CHF caused a two- to sixfold increase (P < 0.05) in diaphragm mRNA and protein levels of several Nox2 subunits, with p47... being upregulated and hyperphosphorylated. CHF increased diaphragm extracellular oxidant emission in wild-type but not p47... knockout mice. Diaphragm isometric force, shortening velocity, and peak power were decreased by 20-50% in CHF wild-type mice (P < 0.05), whereas p47... knockout mice were protected from impairments in diaphragm contractile function elicited by CHF. Our experiments show that p47... is upregulated and involved in the increased oxidants and contractile dysfunction in CHF diaphragm. These findings suggest that a p47...-dependent NAD(P)H oxidase mediates the increase in diaphragm oxidants and contractile dysfunction in CHF. (ProQuest: ... denotes formulae/symbols omitted.)
ISSN:1040-0605
1522-1504