Document Detail


Reactive nitrogen species block cell cycle re-entry through sustained production of hydrogen peroxide.
MedLine Citation:
PMID:  12600834     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Endogenous sources of reactive nitrogen species (RNS) act as second messengers in a variety of cell signaling events, whereas environmental sources of RNS like nitrogen dioxide (NO2) inhibit cell survival and growth through covalent modification of cellular macromolecules. To examine the effects of RNS on cell cycle progression, murine type II alveolar C10 cells arrested in G0 by serum deprivation were exposed to either NO2 or SIN-1, a generator of RNS, during cell cycle re-entry. In serum-stimulated cells, RNS did not prevent the immediate early gene response by AP-1, but rather blocked cyclin D1 gene expression, resulting cell cycle arrest at the boundary between G0 and G1. Dichlorofluorescin diacetate (DCF) fluorescence indicated that RNS induced sustained production of intracellular hydrogen peroxide (H2O2), which normally is produced only transiently in response to serum growth factors. Loading cells with catalase did not diminish the formation of 3-nitrotyrosine on the cell surface, but rather prevented enhanced DCF fluorescence and rescued cyclin D1 expression and S phase entry. These studies indicate environmental RNS interfere with cell cycle re-entry through an H2O2-dependent mechanism that influences expression of cyclin D1 and progression from G0 to the G1 phase of the cell cycle.
Authors:
Ziqiang Yuan; Harriet Schellekens; Loraine Warner; Yvonne Janssen-Heininger; Peter Burch; Nicholas H Heintz
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Publication Detail:
Type:  Journal Article; Research Support, U.S. Gov't, P.H.S.     Date:  2003-01-10
Journal Detail:
Title:  American journal of respiratory cell and molecular biology     Volume:  28     ISSN:  1044-1549     ISO Abbreviation:  Am. J. Respir. Cell Mol. Biol.     Publication Date:  2003 Jun 
Date Detail:
Created Date:  2003-05-22     Completed Date:  2003-07-10     Revised Date:  2007-11-14    
Medline Journal Info:
Nlm Unique ID:  8917225     Medline TA:  Am J Respir Cell Mol Biol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  705-12     Citation Subset:  IM    
Affiliation:
Department of Pathology, University of Vermont College of Medicine, Burlington VT 05465, USA.
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MeSH Terms
Descriptor/Qualifier:
Animals
Catalase / metabolism,  pharmacology
Cell Cycle / drug effects,  physiology*
Cells, Cultured
Cyclin D1 / drug effects,  genetics
Epithelial Cells / drug effects,  metabolism
Fluoresceins / analysis,  metabolism
Gene Expression Regulation / drug effects
Hydrogen Peroxide / metabolism*,  pharmacology
Mice
Molsidomine / analogs & derivatives*,  pharmacology
Nitric Oxide Donors / pharmacology
Nitrogen Dioxide / metabolism,  pharmacology*
Oxidants / metabolism*,  pharmacology
Pulmonary Alveoli / cytology,  metabolism
Signal Transduction / drug effects,  physiology
Superoxide Dismutase / metabolism,  pharmacology
Transcription Factor AP-1 / drug effects,  genetics
Tyrosine / analogs & derivatives*,  metabolism
Grant Support
ID/Acronym/Agency:
ES09673/ES/NIEHS NIH HHS
Chemical
Reg. No./Substance:
0/Fluoresceins; 0/Nitric Oxide Donors; 0/Oxidants; 0/Transcription Factor AP-1; 10102-44-0/Nitrogen Dioxide; 136601-57-5/Cyclin D1; 2044-85-1/diacetyldichlorofluorescein; 25717-80-0/Molsidomine; 33876-97-0/3-morpholino-sydnonimine; 3604-79-3/3-nitrotyrosine; 55520-40-6/Tyrosine; 7722-84-1/Hydrogen Peroxide; EC 1.11.1.6/Catalase; EC 1.15.1.1/Superoxide Dismutase

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


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