Document Detail


Role of components of the phagocytic NADPH oxidase in oxygen sensing.
MedLine Citation:
PMID:  12235036     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
It has been hypothesized that O(2) sensing in type I cells of the carotid body and erythropoietin (EPO)-producing cells of the kidney involves protein components identical to the NADPH oxidase system responsible for the respiratory burst of phagocytes. In the present study, we evaluated O(2) sensing in mice with null mutant genotypes for two components of the phagocytic oxidase. Whole body plethysmography was used to study unanesthetized, unrestrained mice. When exposed to an acute hypoxic stimulus, gp91(phox)-null mutant and wild-type mice increased their minute ventilation by similar amounts. In contrast, p47(phox)-null mutant mice demonstrated increases in minute ventilation in response to hypoxia that exceeded that of their wild-type counterparts: 98.0 +/- 18.0 vs. 20.0 +/- 13.0% (n = 11, P = 0.003). In vitro recordings of carotid sinus nerve (CSN) activity demonstrated that resting (basal) neural activity was marginally elevated in p47(phox)-null mutant mice. With hypoxic challenge, mean CSN discharge was 1.5-fold greater in p47(phox)-null mutant than in wild-type mice: 109.61 +/- 13.29 vs. 72.54 +/- 7.65 impulses/s (n = 8 and 7, respectively, P = 0.026). Consequently, the hypoxia-evoked CSN discharge (stimulus-basal) was approximately 58% larger in p47(phox)-null mutant mice. Quantities of EPO mRNA in kidney were similar in gp91(phox)- and p47(phox)-null mutant mice and their respective wild-type controls exposed to hypobaric hypoxia for 72 h. These findings confirm the previous observation that absence of the gp91(phox) component of the phagocytic NADPH oxidase does not alter the O(2)-sensing mechanism of the carotid body. However, absence of the p47(phox) component significantly potentiates ventilatory and chemoreceptor responses to hypoxia. O(2) sensing in EPO-producing cells of the kidney appears to be independent of the gp91(phox) and p47(phox) components of the phagocytic NADPH oxidase.
Authors:
K A Sanders; K M Sundar; L He; B Dinger; S Fidone; J R Hoidal
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Publication Detail:
Type:  Journal Article; Research Support, U.S. Gov't, Non-P.H.S.; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  Journal of applied physiology (Bethesda, Md. : 1985)     Volume:  93     ISSN:  8750-7587     ISO Abbreviation:  J. Appl. Physiol.     Publication Date:  2002 Oct 
Date Detail:
Created Date:  2002-09-17     Completed Date:  2003-02-21     Revised Date:  2008-11-21    
Medline Journal Info:
Nlm Unique ID:  8502536     Medline TA:  J Appl Physiol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  1357-64     Citation Subset:  IM    
Affiliation:
Medical Service, Department of Veterans Affairs Medical Center, University of Utah School of Medicine, Salt Lake City, Utah 84132, USA.
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MeSH Terms
Descriptor/Qualifier:
Animals
Anoxia / genetics,  metabolism,  physiopathology*
Carotid Sinus / innervation
Chemoreceptor Cells / physiopathology*
Erythropoietin / genetics
Gene Expression
Kidney / physiopathology
Membrane Glycoproteins / metabolism
Mice
Mice, Inbred C57BL
NADPH Oxidase / metabolism*
Nervous System / physiopathology
Oxygen / metabolism*
Phagocytes / enzymology,  physiology*
Phosphoproteins / metabolism
Respiration
Rest
Grant Support
ID/Acronym/Agency:
NS-07938/NS/NINDS NIH HHS; NS-12636/NS/NINDS NIH HHS; P50 HL-50153/HL/NHLBI NIH HHS
Chemical
Reg. No./Substance:
0/CYBB protein, human; 0/Membrane Glycoproteins; 0/Phosphoproteins; 11096-26-7/Erythropoietin; 7782-44-7/Oxygen; EC 1.6.3.1/NADPH Oxidase; EC 1.6.3.1/neutrophil cytosolic factor 1

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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