Document Detail

High levels of catalase and glutathione peroxidase activity dampen H2O2 signaling in human alveolar macrophages.
MedLine Citation:
PMID:  14962975     Owner:  NLM     Status:  MEDLINE    
Results are presented which support the hypothesis that adequate steady-state levels of hydrogen peroxide (H2O2) are required to overcome the effects of high catalase and glutathione peroxidase (GPx) expression for p38 mitogen-activated protein (MAP) kinase activation and tumor necrosis factor (TNF)-alpha gene expression in human alveolar macrophages stimulated with asbestos. We found significant differences in the types and amounts of reactive oxygen species generated in human blood monocytes compared with human alveolar macrophages. This difference in reactive oxygen species production is related, in part, to the differences in antioxidant enzyme expression and activity. Most importantly, catalase and GPx activities were significantly increased in alveolar macrophages compared with blood monocytes. Asbestos activated the p38 MAP kinase and induced TNF-alpha gene expression only in blood monocytes. Increasing the steady-state levels of H2O2 by using polyethylene glycol superoxide dismutase, an antioxidant that crosses the cell membrane, or aminotriazole, an irreversible inhibitor of catalase, allowed the p38 MAP kinase to be activated in alveolar macrophages. In addition, asbestos-stimulated macrophages cultured with polyethylene glycol superoxide dismutase had a significant increase in gene expression mediated by the TNF-alpha promoter. These results demonstrate that high catalase and GPx activity in human alveolar macrophages limits the effectiveness of H2O2 to act as a mediator of inflammatory gene expression.
A Brent Carter; Linda A Tephly; Sujatha Venkataraman; Larry W Oberley; Yuping Zhang; Garry R Buettner; Douglas R Spitz; Gary W Hunninghake
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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.     Date:  2004-02-12
Journal Detail:
Title:  American journal of respiratory cell and molecular biology     Volume:  31     ISSN:  1044-1549     ISO Abbreviation:  Am. J. Respir. Cell Mol. Biol.     Publication Date:  2004 Jul 
Date Detail:
Created Date:  2004-06-21     Completed Date:  2004-08-24     Revised Date:  2009-11-19    
Medline Journal Info:
Nlm Unique ID:  8917225     Medline TA:  Am J Respir Cell Mol Biol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  43-53     Citation Subset:  IM    
Department of Medicine, University of Iowa Roy J. and Lucille A Carver College of Medicine, Iowa City Veterans Administration medical Center, Iowa City, IA 52242, USA.
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MeSH Terms
Amitrole / pharmacology
Catalase / metabolism*
Cells, Cultured
Gene Expression Regulation, Enzymologic / drug effects,  genetics
Glutathione Peroxidase / metabolism*
Hydrogen Peroxide / metabolism*
Lung / enzymology,  metabolism
Macrophages, Alveolar / drug effects,  enzymology,  metabolism*
Mitogen-Activated Protein Kinases / genetics
Monocytes / drug effects,  enzymology
Oxidative Stress / drug effects,  physiology
Pneumonia / enzymology,  metabolism*
Promoter Regions, Genetic / drug effects,  genetics
RNA, Messenger / drug effects,  metabolism
Reactive Oxygen Species / metabolism
Signal Transduction / drug effects,  physiology
Superoxide Dismutase / metabolism,  pharmacology
Tumor Necrosis Factor-alpha / genetics
Up-Regulation / drug effects,  physiology
p38 Mitogen-Activated Protein Kinases
Grant Support
Reg. No./Substance:
0/RNA, Messenger; 0/Reactive Oxygen Species; 0/Tumor Necrosis Factor-alpha; 1332-21-4/Asbestos; 61-82-5/Amitrole; 7722-84-1/Hydrogen Peroxide; EC; EC Peroxidase; EC Dismutase; EC Protein Kinases; EC Mitogen-Activated Protein Kinases

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