Document Detail


Phospholipid hydroperoxide glutathione peroxidase induces a delay in G1 of the cell cycle.
MedLine Citation:
PMID:  12868489     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Phospholipid hydroperoxide glutathione peroxidase (PhGPx) is an antioxidant enzyme that reduces cellular phospholipid hydroperoxides (PLOOHs) to alcohols. Cellular peroxide tone has been implicated in cell growth and differentiation. By reducing the PLOOH level in the cell membrane, PhGPx regulates the peroxide tone and thereby might be involved in cell growth. We hypothesized that overexpression of PhGPx in human breast cancer cells would decrease their growth rate. We stably transfected MCF-7 cells (Wt) with L-PhGPx and measured cell doubling time, plating efficiency, and cell cycle phase transit times. P-4 cells (8-fold increase in PhGPx activity) showed a 2-fold increase in doubling time; doubling time increased directly with PhGPx activity (r = 0.95). The higher the PhGPx activity, the lower the plating efficiency (r = -0.86). The profile of other antioxidant enzymes was unchanged. Overexpression of PhGPx lowered the steady-state level of PLOOH (by > 60%). Results from bromodeoxyuridine pulse-chase experiments and flow cytometry indicate that PhGPx induced a delay in MCF-7 proliferation that was primarily due to a slower progression from G1 to S. These results support the hypothesis that PhGPx plays a regulatory role in the progression of MCF-7 cells from G1 to S possibly by regulating the steady-state levels of PLOOH. These data suggest that PhGPx can lower the peroxide tone, which might change the cellular redox environment resulting in a delay in G1 transit. Thus, PhGPx could be an important factor in cell growth.
Authors:
Hong P Wang; Freya Q Schafer; Prabhat C Goswami; Larry W Oberley; Garry R Buettner
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Publication Detail:
Type:  Journal Article; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  Free radical research     Volume:  37     ISSN:  1071-5762     ISO Abbreviation:  Free Radic. Res.     Publication Date:  2003 Jun 
Date Detail:
Created Date:  2003-07-18     Completed Date:  2003-12-16     Revised Date:  2007-11-14    
Medline Journal Info:
Nlm Unique ID:  9423872     Medline TA:  Free Radic Res     Country:  England    
Other Details:
Languages:  eng     Pagination:  621-30     Citation Subset:  IM    
Affiliation:
Free Radical and Radiation Biology and The Holden Comprehensive Cancer Center, The University of Iowa, Iowa City, IA 52242-1101, USA.
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MeSH Terms
Descriptor/Qualifier:
Antioxidants / metabolism
Blotting, Western
Bromodeoxyuridine / pharmacology
Catalase / metabolism
Cell Cycle
Cell Differentiation
Cell Line, Tumor
Flow Cytometry
G1 Phase*
Glutathione / metabolism
Glutathione Peroxidase / metabolism*
Glutathione Reductase / metabolism
Humans
Immunoblotting
Lipid Metabolism
Lipid Peroxides / metabolism
Models, Chemical
Oxidation-Reduction
Protein Biosynthesis
Superoxide Dismutase / metabolism
Time Factors
Transfection
Grant Support
ID/Acronym/Agency:
CA66081/CA/NCI NIH HHS; CA69593/CA/NCI NIH HHS; CA81090/CA/NCI NIH HHS
Chemical
Reg. No./Substance:
0/Antioxidants; 0/Lipid Peroxides; 59-14-3/Bromodeoxyuridine; 70-18-8/Glutathione; EC 1.11.1.12/phospholipid-hydroperoxide glutathione peroxidase; EC 1.11.1.6/Catalase; EC 1.11.1.9/Glutathione Peroxidase; EC 1.15.1.1/Superoxide Dismutase; EC 1.8.1.7/Glutathione Reductase

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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