| Peroxiredoxin 6, a 1-Cys peroxiredoxin, functions in antioxidant defense and lung phospholipid metabolism. | |
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MedLine Citation:
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PMID: 15890616 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Peroxiredoxin 6 (Prdx6), a bifunctional 25-kDa protein with both GSH peroxidase and phospholipase A2 activities, is the only mammalian 1-Cys member of the peroxiredoxin superfamily and is expressed in all major organs, with a particularly high level in lung. Prdx6 uses GSH as an electron donor to reduce H2O2 and other hydroperoxides including phospholipid hydroperoxides at approximately 5 micromol/mg protein/min with K1 approximately 3 x 10(6) M(-1) s(-1). Oxidation of the Cys47 to a sulfenic acid during catalysis requires piGST-catalyzed glutathionylation and reduction with GSH to complete the enzymatic cycle. Prdx6 stably overexpressed in cells protected against oxidative stress, whereas antisense treatment resulted in oxidant stress and apoptosis. Adenoviral-mediated overexpression of Prdx6 in mouse lungs protected against the toxicity of hyperoxia, whereas Prdx6-null mice were more sensitive to the effects of hyperoxia or paraquat. We postulate that Prdx6 functions in antioxidant defense mainly by facilitating repair of damaged cell membranes via reduction of peroxidized phospholipids. The PLA2 activity of Prdx6 is Ca2+ independent and maximal at acidic pH. Inhibition of PLA2 activity results in alterations of lung surfactant phospholipid synthesis and turnover. Thus, Prdx6, a unique mammalian peroxiredoxin, is an important antioxidant enzyme and has a major role in lung phospholipid metabolism. |
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Authors:
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Yefim Manevich; Aron B Fisher |
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Publication Detail:
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Type: Journal Article; Research Support, N.I.H., Extramural; Research Support, U.S. Gov't, P.H.S.; Review |
Journal Detail:
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Title: Free radical biology & medicine Volume: 38 ISSN: 0891-5849 ISO Abbreviation: Free Radic. Biol. Med. Publication Date: 2005 Jun |
Date Detail:
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Created Date: 2005-05-13 Completed Date: 2005-10-06 Revised Date: 2007-11-15 |
Medline Journal Info:
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Nlm Unique ID: 8709159 Medline TA: Free Radic Biol Med Country: United States |
Other Details:
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Languages: eng Pagination: 1422-32 Citation Subset: IM |
Affiliation:
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Institute for Environmental Medicine, University of Pennsylvania Medical Center, Philadelphia, PA 19104, USA. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Animals Anoxia / metabolism Antioxidants / chemistry, metabolism Apoptosis Binding Sites Calcium / metabolism Cell Line, Tumor Electrons Glutathione / chemistry, metabolism Humans Hydrogen Peroxide / pharmacology Hydrogen-Ion Concentration Kinetics Lung / metabolism Mice Mice, Inbred C57BL Models, Chemical Models, Molecular Oxidative Stress Oxygen / metabolism Peroxidases / biosynthesis*, chemistry, metabolism, physiology Peroxiredoxin VI Peroxiredoxins Phospholipases A / chemistry Phospholipases A2 RNA, Messenger / metabolism Structure-Activity Relationship Time Factors Tissue Distribution |
| Grant Support | |
ID/Acronym/Agency:
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HL19737/HL/NHLBI NIH HHS; HL65543/HL/NHLBI NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Antioxidants; 0/RNA, Messenger; 70-18-8/Glutathione; 7440-70-2/Calcium; 7722-84-1/Hydrogen Peroxide; 7782-44-7/Oxygen; EC 1.11.1.-/Peroxidases; EC 1.11.1.15/PRDX6 protein, human; EC 1.11.1.15/Peroxiredoxin VI; EC 1.11.1.15/Peroxiredoxins; EC 1.11.1.15/Prdx6 protein, mouse; EC 3.1.1.-/Phospholipases A; EC 3.1.1.4/Phospholipases A2 |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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