Document Detail


Protection of cells in physiological oxygen tensions against DNA damage-induced apoptosis.
MedLine Citation:
PMID:  20228054     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Oxygen availability has important effects on cell physiology. Although hyperoxic and hypoxic stresses have been well characterized, little is known about cellular functions in the oxygen levels commonly found in vivo. Here, we show that p53-dependent apoptosis in response to different DNA-damaging agents was reduced when normal and cancer cells were cultured at physiological oxygen tensions instead of the usual atmospheric levels. Different from what has been described in hypoxia, this was neither determined by decreases in p53 induction or its transactivation activity, nor by differences in the intracellular accumulation of reactive oxygen species. At these physiological oxygen levels, we found a constitutive activation of the ERK1/2 MAPK in all the models studied. Inhibition of this signaling pathway reversed the protective effect in some but not all cell lines. We conclude that a stress-independent constitutive activation of prosurvival pathways, including but probably not limited to MAPK, can protect cells in physiological oxygen tensions against genotoxic stress. Our results underscore the need of considering the impact of oxygen levels present in the tissue microenvironment when studying cell sensitivity to treatments such as chemotherapy and radiotherapy.
Authors:
Samantha Carrera; Petra J de Verdier; Zahid Khan; Bo Zhao; Alka Mahale; Karen J Bowman; Muri Zainol; George D D Jones; Sam W Lee; Stuart A Aaronson; Salvador Macip
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2010-03-12
Journal Detail:
Title:  The Journal of biological chemistry     Volume:  285     ISSN:  1083-351X     ISO Abbreviation:  J. Biol. Chem.     Publication Date:  2010 Apr 
Date Detail:
Created Date:  2010-04-26     Completed Date:  2010-05-27     Revised Date:  2014-09-13    
Medline Journal Info:
Nlm Unique ID:  2985121R     Medline TA:  J Biol Chem     Country:  United States    
Other Details:
Languages:  eng     Pagination:  13658-65     Citation Subset:  IM    
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MeSH Terms
Descriptor/Qualifier:
Apoptosis*
Cell Hypoxia / genetics
Cell Line, Tumor
Cell Survival / genetics
DNA Damage*
Humans
MAP Kinase Signaling System
Mitogen-Activated Protein Kinase 3 / metabolism
Models, Biological*
Oxygen / metabolism*
Reactive Oxygen Species / metabolism*
Tumor Suppressor Protein p53 / genetics,  metabolism*
Grant Support
ID/Acronym/Agency:
C13560/A4661//Cancer Research UK; CA78356/CA/NCI NIH HHS; CA80058/CA/NCI NIH HHS; CA82211/CA/NCI NIH HHS; CA85214/CA/NCI NIH HHS; R01 CA085681/CA/NCI NIH HHS; R01 CA149477/CA/NCI NIH HHS
Chemical
Reg. No./Substance:
0/Reactive Oxygen Species; 0/TP53 protein, human; 0/Tumor Suppressor Protein p53; EC 2.7.11.24/Mitogen-Activated Protein Kinase 3; S88TT14065/Oxygen
Comments/Corrections

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


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