Document Detail

Genetic requirement of p47phox for superoxide production by murine microglia.
MedLine Citation:
PMID:  11156938     Owner:  NLM     Status:  MEDLINE    
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.
M C Lavigne; H L Malech; S M Holland; T L Leto
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Publication Detail:
Type:  Journal Article     Date:  2000-12-08
Journal Detail:
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:
Created Date:  2001-02-22     Completed Date:  2001-03-22     Revised Date:  2012-02-15    
Medline Journal Info:
Nlm Unique ID:  8804484     Medline TA:  FASEB J     Country:  United States    
Other Details:
Languages:  eng     Pagination:  285-7     Citation Subset:  IM    
Laboratory of Host Defenses, NIAID, NIH, Bethesda, MD 20892, USA.
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MeSH Terms
Animals, Newborn
Cells, Cultured
Luminescent Measurements
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
Zymosan / pharmacology
Reg. No./Substance:
0/Phosphoproteins; 0/Recombinant Proteins; 11062-77-4/Superoxides; 16561-29-8/Tetradecanoylphorbol Acetate; 9010-72-4/Zymosan; EC Oxidase; EC cytosolic factor 1; EC Dehydrogenase

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