Document Detail

The effects of disruption of genes for peroxiredoxin-2, glutathione peroxidase-1, and catalase on erythrocyte oxidative metabolism.
MedLine Citation:
PMID:  19969073     Owner:  NLM     Status:  MEDLINE    
Peroxiredoxin-2 (Prdx2), a potent peroxide reductant, is the third most abundant protein in the erythrocyte and might be expected to play a major role in the cell's oxidative defenses. However, in this study, experiments with erythrocytes from mice with a disrupted Prdx2 gene found that the cells were not more sensitive to exogenous H(2)O(2) or organic peroxides than wild type. Intraerythrocytic H(2)O(2) was increased, however, indicating an important role for Prdx2 in detoxifying endogenously generated H(2)O(2). These results are consistent with proposals that red cell Prdx2 acts stoichiometrically, not catalytically, in reducing peroxides. Additional experiments with mice with disrupted catalase or glutathione peroxidase (Gpx1) genes showed that Gpx1 is the only erythrocyte enzyme that reduces organic peroxides. Catalase(-/-) cells were readily oxidized by exogenous H(2)O(2). Cells lacking both catalase and Gpx1 were more sensitive to exogenous H(2)O(2) than cells lacking only catalase. A kinetic model proposed earlier to rationalize results with Gpx1(-/-) erythrocytes also fits the data with Prdx2(-/-) cells and indicates that although Gpx1 and Prdx2 both participate in removing endogenous H(2)O(2), Prdx2 plays a larger role. Although the rate of H(2)O(2) production in the red cell is quite low, Prdx2-deficient mice are anemic, suggesting an important role in erythropoiesis.
Robert M Johnson; Ye-Shih Ho; Dae-Yeul Yu; Frans A Kuypers; Yaddanapudi Ravindranath; Gerard W Goyette
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2009-12-04
Journal Detail:
Title:  Free radical biology & medicine     Volume:  48     ISSN:  1873-4596     ISO Abbreviation:  Free Radic. Biol. Med.     Publication Date:  2010 Feb 
Date Detail:
Created Date:  2010-02-03     Completed Date:  2010-06-03     Revised Date:  2013-05-31    
Medline Journal Info:
Nlm Unique ID:  8709159     Medline TA:  Free Radic Biol Med     Country:  United States    
Other Details:
Languages:  eng     Pagination:  519-25     Citation Subset:  IM    
Copyright Information:
Copyright 2009 Elsevier Inc. All rights reserved.
Department of Biochemistry and Molecular Biology, Wayne State University, Detroit, MI 48201, USA.
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MeSH Terms
Catalase / genetics*,  metabolism
Dose-Response Relationship, Drug
Erythrocytes / enzymology*,  metabolism
Glutathione Peroxidase / genetics*,  metabolism
Hydrogen Peroxide / chemistry
Mice, Inbred C57BL
Oxidative Stress
Oxygen / metabolism
Peroxiredoxins / genetics*,  metabolism
Grant Support
Reg. No./Substance:
7722-84-1/Hydrogen Peroxide; 7782-44-7/Oxygen; EC 1.11.1.-/glutathione peroxidase GPX1; EC; EC; EC Peroxidase

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