| Protection of cells in physiological oxygen tensions against DNA damage-induced apoptosis. | |
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MedLine Citation:
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PMID: 20228054 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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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. |
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Authors:
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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:
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Type: Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't Date: 2010-03-12 |
Journal Detail:
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Title: The Journal of biological chemistry Volume: 285 ISSN: 1083-351X ISO Abbreviation: J. Biol. Chem. Publication Date: 2010 Apr |
Date Detail:
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Created Date: 2010-04-26 Completed Date: 2010-05-27 Revised Date: 2011-07-28 |
Medline Journal Info:
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Nlm Unique ID: 2985121R Medline TA: J Biol Chem Country: United States |
Other Details:
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Languages: eng Pagination: 13658-65 Citation Subset: IM |
Affiliation:
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Department of Biochemistry, University of Leicester, Lancaster Road, Leicester LE1 9HN, United Kingdom. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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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:
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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 CA085681-10/CA/NCI NIH HHS; R01 CA149477-02/CA/NCI NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Reactive Oxygen Species; 0/TP53 protein, human; 0/Tumor Suppressor Protein p53; 7782-44-7/Oxygen; EC 2.7.11.24/Mitogen-Activated Protein Kinase 3 |
| Comments/Corrections | |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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