Document Detail


The roles of peroxidase and phospholipase A2 activities of peroxiredoxin 6 in protecting pulmonary microvascular endothelial cells against peroxidative stress.
MedLine Citation:
PMID:  22067043     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
AIMS: Peroxiredoxin 6 (Prdx6), a bifunctional enzyme with glutathione peroxidase and phospholipase A(2) (PLA(2)) activities, has been demonstrated as playing a critical role in antioxidant defense of the lung. Our aim was to evaluate the relative role of each activity in Prdx6-mediated protection of mouse pulmonary microvascular endothelial cells (PMVECs) against the peroxidative stress of treatment with tert-butyl hydroperoxide (tBOOH).
RESULTS: PMVEC from Prdx6 null mice showed increased lethality on tBOOH exposure (50-200 μM) compared with wild-type (WT) controls. Treatment with 1-hexadecyl-3-trifluoroethylglycero-sn-2-phosphomethanol (MJ33), a Prdx6 PLA(2) activity inhibitor, increased the sensitivity of WT cells to peroxidative stress, but did not further sensitize Prdx6 null cells. Lethality in Prdx6 null PMVEC was "rescued" by transfection with a construct leading to the expression of WT rat Prdx6. Expression of mutant Prdx6 with either peroxidase activity or PLA(2) activity alone each partially rescued the survival of Prdx6 null cells, while constructs with both active sites mutated failed to rescue. Co-transfection with two different constructs, each expressing one activity, rescued cells as well as the WT construct.
INNOVATION AND CONCLUSION: Contrary to the general assumption that the peroxidase activity is the main mechanism for Prdx6 antioxidant function, these results indicate that the PLA(2) activity also plays a substantial role in protecting cells against oxidant stress caused by an exogenous hydroperoxide.
Authors:
Yu-Chin Lien; Sheldon I Feinstein; Chandra Dodia; Aron B Fisher
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural     Date:  2011-12-23
Journal Detail:
Title:  Antioxidants & redox signaling     Volume:  16     ISSN:  1557-7716     ISO Abbreviation:  Antioxid. Redox Signal.     Publication Date:  2012 Mar 
Date Detail:
Created Date:  2012-01-18     Completed Date:  2012-09-14     Revised Date:  2013-11-06    
Medline Journal Info:
Nlm Unique ID:  100888899     Medline TA:  Antioxid Redox Signal     Country:  United States    
Other Details:
Languages:  eng     Pagination:  440-51     Citation Subset:  IM    
Affiliation:
Institute for Environmental Medicine, University of Pennsylvania, School of Medicine, Philadelphia, Pennsylvania, USA.
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MeSH Terms
Descriptor/Qualifier:
Animals
Cells, Cultured
Endothelial Cells / metabolism*
Lipid Peroxidation
Lung / blood supply*,  cytology
Mice
Mice, Knockout
Microvessels / cytology*
Oxidative Stress*
Peroxidase / metabolism*
Peroxiredoxin VI / deficiency,  metabolism*
Phospholipases A2 / metabolism*
Grant Support
ID/Acronym/Agency:
HL P01-75587/HL/NHLBI NIH HHS; R01 HL105509/HL/NHLBI NIH HHS
Chemical
Reg. No./Substance:
EC 1.11.1.15/Peroxiredoxin VI; EC 1.11.1.15/Prdx6 protein, mouse; EC 1.11.1.7/Peroxidase; EC 3.1.1.4/Phospholipases A2
Comments/Corrections

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