Document Detail


Hydrogen peroxide mediates the cell growth and transformation caused by the mitogenic oxidase Nox1.
MedLine Citation:
PMID:  11331784     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Nox1, a homologue of gp91phox, the catalytic moiety of the superoxide (O(2)(-))-generating NADPH oxidase of phagocytes, causes increased O(2)(-) generation, increased mitotic rate, cell transformation, and tumorigenicity when expressed in NIH 3T3 fibroblasts. This study explores the role of reactive oxygen species (ROS) in regulating cell growth and transformation by Nox1. H(2)O(2) concentration increased approximately 10-fold in Nox1-expressing cells, compared with <2-fold increase in O(2)(-). When human catalase was expressed in Nox1-expressing cells, H(2)O(2) concentration decreased, and the cells reverted to a normal appearance, the growth rate normalized, and cells no longer produced tumors in athymic mice. A large number of genes, including many related to cell cycle, growth, and cancer (but unrelated to oxidative stress), were expressed in Nox1-expressing cells, and more than 60% of these returned to normal levels on coexpression of catalase. Thus, H(2)O(2) in low concentrations functions as an intracellular signal that triggers a genetic program related to cell growth.
Authors:
R S Arnold; J Shi; E Murad; A M Whalen; C Q Sun; R Polavarapu; S Parthasarathy; J A Petros; J D Lambeth
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Publication Detail:
Type:  Journal Article; Research Support, U.S. Gov't, P.H.S.     Date:  2001-05-01
Journal Detail:
Title:  Proceedings of the National Academy of Sciences of the United States of America     Volume:  98     ISSN:  0027-8424     ISO Abbreviation:  Proc. Natl. Acad. Sci. U.S.A.     Publication Date:  2001 May 
Date Detail:
Created Date:  2001-05-10     Completed Date:  2001-06-14     Revised Date:  2009-11-18    
Medline Journal Info:
Nlm Unique ID:  7505876     Medline TA:  Proc Natl Acad Sci U S A     Country:  United States    
Other Details:
Languages:  eng     Pagination:  5550-5     Citation Subset:  IM    
Affiliation:
Department of Biochemistry, Atlanta Veterans Affairs Medical Center and Winship Cancer Institute, Emory University School of Medicine, Atlanta, GA 30322, USA.
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MeSH Terms
Descriptor/Qualifier:
Animals
Base Sequence
Catalase / metabolism
Cell Division / drug effects*,  physiology
Cell Line
Cell Transformation, Neoplastic / drug effects*
DNA Primers
Hydrogen Peroxide / pharmacology*
Mice
Mice, Nude
NADH, NADPH Oxidoreductases / physiology*
Reverse Transcriptase Polymerase Chain Reaction
Grant Support
ID/Acronym/Agency:
CA84138/CA/NCI NIH HHS
Chemical
Reg. No./Substance:
0/DNA Primers; 7722-84-1/Hydrogen Peroxide; EC 1.11.1.6/Catalase; EC 1.6.-/NADH, NADPH Oxidoreductases; EC 1.6.99.-/NADPH oxidase 1
Comments/Corrections

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