| Activation of H+ conductance in neutrophils requires assembly of components of the respiratory burst oxidase but not its redox function. | |
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MedLine Citation:
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PMID: 8163676 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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In phagocytes, superoxide generation by the NADPH oxidase is accompanied by metabolic acid production. Cytoplasmic acidification during this metabolic burst is prevented by a combination of H+ extrusion mechanisms, including a unique H+ conductance. NADPH oxidase is deficient in chronic granulomatous disease (CGD) patients. The burst of acid production is absent in CGD patients lacking the 47-kD (p47-phox) or the 91-kD (gp91-phox) subunits of the oxidase. Activation of the H+ conductance is also defective in these patients suggesting that (a) the oxidase itself undertakes H+ translocation or (b) oxidase assembly is required to stimulate a separate H+ conducting entity. To discern between these possibilities, three rare forms of CGD were studied. In neutrophils expressing nonfunctional cytochrome b, the conductance was activated to near-normal levels, implying that functional oxidase is not required to activate H+ extrusion. CGD cells expressing diminished amounts of cytochrome displayed H+ conductance approaching normal levels, suggesting that the oxidase itself does not translocate H+. Finally, the conductance was only partially inhibited in patients lacking the 67-kD subunit, indicating that this component is not essential for stimulation of H+ transport. We propose that normal assembly of the oxidase subunits is required for optimal activation of a closely associated but distinct H+ conducting entity. |
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Authors:
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A Nanda; J T Curnutte; S Grinstein |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, P.H.S. |
Journal Detail:
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Title: The Journal of clinical investigation Volume: 93 ISSN: 0021-9738 ISO Abbreviation: J. Clin. Invest. Publication Date: 1994 Apr |
Date Detail:
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Created Date: 1994-05-20 Completed Date: 1994-05-20 Revised Date: 2009-11-18 |
Medline Journal Info:
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Nlm Unique ID: 7802877 Medline TA: J Clin Invest Country: UNITED STATES |
Other Details:
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Languages: eng Pagination: 1770-5 Citation Subset: AIM; IM |
Affiliation:
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Division of Cell Biology, Hospital for Sick Children, Toronto, Canada. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Female Granulomatous Disease, Chronic / metabolism* Humans Ion Transport Male NADH, NADPH Oxidoreductases / physiology* NADPH Oxidase Neutrophils / metabolism* Oxidation-Reduction Point Mutation Protons Respiratory Burst Tetradecanoylphorbol Acetate / pharmacology |
| Grant Support | |
ID/Acronym/Agency:
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AI24838/AI/NIAID NIH HHS; RR00833/RR/NCRR NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Protons; 16561-29-8/Tetradecanoylphorbol Acetate; EC 1.6.-/NADH, NADPH Oxidoreductases; EC 1.6.3.1/NADPH Oxidase |
| Comments/Corrections | |
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