Source:http://linkedlifedata.com/resource/pubmed/id/14514662
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rdf:type | |
lifeskim:mentions | |
pubmed:issue |
1
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pubmed:dateCreated |
2003-12-24
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pubmed:abstractText |
The epithelial cell line I407 up-regulates cyclooxygenase-2 (COX-2) mRNA and protein expression following ionizing radiation exposure. Prostaglandin E2 (PGE2) production is concomitantly up-regulated. Irradiation of I407 cells also results in phosphorylation of the p38 mitogen-activated protein kinase and the p38 inhibitor SB203580 abrogates radiation-induced PGE2 synthesis. Wild-type p38alpha (p38alphaWT) and dominant-negative p38alpha (p38alphaDN) stable-transfectant clones of I407 cells were used to examine the role of the p38 mitogen-activated protein kinase pathway in the events controlling PGE2 synthesis after ionizing radiation. Treatment of p38alphaWT clones with gamma-radiation resulted in increased COX-2 protein levels and PGE2 synthesis similar to treated control-transfected cells. In contrast, the p38alphaDN clones failed to up-regulate COX-2 protein or increase PGE2 synthesis when irradiated. Exogenous arachidonate did not restore PGE2 synthesis by p38alphaDN cells. Radiation increased COX-2 mRNA stability and the p38 inhibitor SB203580 attenuated COX-2 mRNA stability in irradiated I407 cells. In contrast, irradiation had no effect on transcription from a COX-2 promoter/luciferase reporter plasmid in the presence or absence of SB203580. The data demonstrate a crucial role for p38alpha in COX-2 expression and PGE2 synthesis in an irradiated transformed epithelial cell line. Furthermore, they indicate that p38 activity is required at a step distal to arachidonate release, most probably COX-2 up-regulation, since exogenous arachidonate did not restore PGE2 synthesis.
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pubmed:grant | |
pubmed:language |
eng
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pubmed:journal | |
pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Cyclooxygenase 2,
http://linkedlifedata.com/resource/pubmed/chemical/Dinoprostone,
http://linkedlifedata.com/resource/pubmed/chemical/Isoenzymes,
http://linkedlifedata.com/resource/pubmed/chemical/Membrane Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Mitogen-Activated Protein Kinases,
http://linkedlifedata.com/resource/pubmed/chemical/PTGS2 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Prostaglandin-Endoperoxide Synthases,
http://linkedlifedata.com/resource/pubmed/chemical/p38 Mitogen-Activated Protein...
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pubmed:status |
MEDLINE
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pubmed:month |
Jan
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pubmed:issn |
0143-3334
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pubmed:author | |
pubmed:issnType |
Print
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pubmed:volume |
25
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
37-45
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pubmed:dateRevised |
2009-11-19
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pubmed:meshHeading |
pubmed-meshheading:14514662-Cells, Cultured,
pubmed-meshheading:14514662-Cyclooxygenase 2,
pubmed-meshheading:14514662-Dinoprostone,
pubmed-meshheading:14514662-Epithelial Cells,
pubmed-meshheading:14514662-Gene Expression Regulation, Enzymologic,
pubmed-meshheading:14514662-Humans,
pubmed-meshheading:14514662-Isoenzymes,
pubmed-meshheading:14514662-Membrane Proteins,
pubmed-meshheading:14514662-Mitogen-Activated Protein Kinases,
pubmed-meshheading:14514662-Promoter Regions, Genetic,
pubmed-meshheading:14514662-Prostaglandin-Endoperoxide Synthases,
pubmed-meshheading:14514662-Transcription, Genetic,
pubmed-meshheading:14514662-Up-Regulation,
pubmed-meshheading:14514662-p38 Mitogen-Activated Protein Kinases
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pubmed:year |
2004
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pubmed:articleTitle |
Ionizing radiation up-regulates cyclooxygenase-2 in I407 cells through p38 mitogen-activated protein kinase.
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pubmed:affiliation |
Division of Gastroenterology, Washington University School of Medicine, St Louis, MO 63110, USA. stensnlb@im.wustl.edu
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pubmed:publicationType |
Journal Article,
Research Support, U.S. Gov't, P.H.S.
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