| Genetic requirement of p47phox for superoxide production by murine microglia. | |
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MedLine Citation:
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PMID: 11156938 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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An NADPH oxidase is thought to function in microglial cells of the central nervous system. These conclusions are based on pharmacological and immunochemical evidence, although these approaches are indirect and raise issues of specificity. For example, diphenyleneiodonium inhibits a variety of flavoenzymes, including xanthine oxidase, NADH dehydrogenase, and NADPH oxidase. Here, we provide genetic evidence that p47phox, an essential component of the phagocyte NADPH oxidase, is required for superoxide anion release from microglia. Microglia derived from newborn wild-type mice, but not from newborn p47phox-deficient (knockout; -/-) mice, produced superoxide after stimulation by opsonized zymosan or phorbol myristate acetate. Endogenous p47phox was detected only in wild-type microglia, consistent with selective superoxide production in these cells. Superoxide release was restored in p47phox-deficient microglia that were retrovirally transduced with human p47phox cDNA. Similar kinetics of superoxide generation were observed, consistent with the same enzyme functioning in wild-type and restored microglia. Immuno-detection of p47phox in transduced cells confirmed that restoration of superoxide release correlated with production of recombinant protein. These data provide genetic proof that p47phox is necessary for superoxide release by microglial cells and indicate that a system related to the phagocyte oxidase is active in these cells. |
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Authors:
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M C Lavigne; H L Malech; S M Holland; T L Leto |
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Publication Detail:
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Type: Journal Article Date: 2000-12-08 |
Journal Detail:
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Title: FASEB journal : official publication of the Federation of American Societies for Experimental Biology Volume: 15 ISSN: 0892-6638 ISO Abbreviation: FASEB J. Publication Date: 2001 Feb |
Date Detail:
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Created Date: 2001-02-22 Completed Date: 2001-03-22 Revised Date: 2012-02-15 |
Medline Journal Info:
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Nlm Unique ID: 8804484 Medline TA: FASEB J Country: United States |
Other Details:
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Languages: eng Pagination: 285-7 Citation Subset: IM |
Affiliation:
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Laboratory of Host Defenses, NIAID, NIH, Bethesda, MD 20892, USA. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Animals Animals, Newborn Cells, Cultured Luminescent Measurements Mice Mice, Knockout Microglia / cytology, drug effects, physiology* NADPH Dehydrogenase / metabolism NADPH Oxidase Nerve Degeneration Phosphoproteins / deficiency, genetics, metabolism* Recombinant Proteins / metabolism Superoxides / metabolism* Tetradecanoylphorbol Acetate / pharmacology Transfection Zymosan / pharmacology |
| Chemical | |
Reg. No./Substance:
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0/Phosphoproteins; 0/Recombinant Proteins; 11062-77-4/Superoxides; 16561-29-8/Tetradecanoylphorbol Acetate; 9010-72-4/Zymosan; EC 1.6.3.1/NADPH Oxidase; EC 1.6.3.1/neutrophil cytosolic factor 1; EC 1.6.99.1/NADPH Dehydrogenase |
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