Source:http://linkedlifedata.com/resource/pubmed/id/17535806
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rdf:type | |
lifeskim:mentions | |
pubmed:issue |
31
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pubmed:dateCreated |
2007-7-30
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pubmed:abstractText |
Arachidonic acid is released by phospholipase A(2) and converted into hundreds of distinct bioactive mediators by a variety of cyclooxygenases (COX), lipoxygenases (LO), and cytochrome P450s. Because of the size and diversity of the eicosanoid class of signaling molecules produced, a thorough and systematic investigation of these biological processes requires the simultaneous quantitation of a large number of eicosanoids in a single analysis. We have developed a robust liquid chromatography/tandem mass spectrometry method that can identify and quantitate over 60 different eicosanoids in a single analysis, and we applied it to agonist-stimulated RAW264.7 murine macrophages. Fifteen different eicosanoids produced through COX and 5-LO were detected either intracellularly or in the media following stimulation with 16 different agonists of Toll-like receptors (TLR), G protein-coupled receptors, and purinergic receptors. No significant differences in the COX metabolite profiles were detected using the different agonists; however, we determined that only agonists creating a sustained Ca(2+) influx were capable of activating the 5-LO pathway in these cells. Synergy between Ca(2+) and TLR pathways was detected and discovered to be independent of NF-kappaB-induced protein synthesis. This demonstrates that TLR induction of protein synthesis and priming for enhanced phospholipase A(2)-mediated eicosanoid production work through two distinct pathways.
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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/Adenosine Triphosphate,
http://linkedlifedata.com/resource/pubmed/chemical/Arachidonate 5-Lipoxygenase,
http://linkedlifedata.com/resource/pubmed/chemical/Calcium,
http://linkedlifedata.com/resource/pubmed/chemical/Eicosanoids,
http://linkedlifedata.com/resource/pubmed/chemical/Lipids,
http://linkedlifedata.com/resource/pubmed/chemical/NF-kappa B,
http://linkedlifedata.com/resource/pubmed/chemical/Phospholipases A,
http://linkedlifedata.com/resource/pubmed/chemical/Prostaglandin-Endoperoxide Synthases,
http://linkedlifedata.com/resource/pubmed/chemical/Tlr4 protein, mouse,
http://linkedlifedata.com/resource/pubmed/chemical/Toll-Like Receptor 4
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pubmed:status |
MEDLINE
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pubmed:month |
Aug
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pubmed:issn |
0021-9258
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pubmed:author | |
pubmed:issnType |
Print
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pubmed:day |
3
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pubmed:volume |
282
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
22834-47
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pubmed:dateRevised |
2007-12-3
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pubmed:meshHeading |
pubmed-meshheading:17535806-Adenosine Triphosphate,
pubmed-meshheading:17535806-Animals,
pubmed-meshheading:17535806-Arachidonate 5-Lipoxygenase,
pubmed-meshheading:17535806-Calcium,
pubmed-meshheading:17535806-Cell Line,
pubmed-meshheading:17535806-Eicosanoids,
pubmed-meshheading:17535806-Gene Expression Regulation,
pubmed-meshheading:17535806-Lipids,
pubmed-meshheading:17535806-Mice,
pubmed-meshheading:17535806-Models, Biological,
pubmed-meshheading:17535806-NF-kappa B,
pubmed-meshheading:17535806-Phospholipases A,
pubmed-meshheading:17535806-Prostaglandin-Endoperoxide Synthases,
pubmed-meshheading:17535806-Time Factors,
pubmed-meshheading:17535806-Toll-Like Receptor 4
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pubmed:year |
2007
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pubmed:articleTitle |
TLR-4 and sustained calcium agonists synergistically produce eicosanoids independent of protein synthesis in RAW264.7 cells.
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pubmed:affiliation |
Department of Chemistry and Biochemistry, School of Medicine, University of California, San Diego, La Jolla, California 92093, USA.
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pubmed:publicationType |
Journal Article,
Research Support, N.I.H., Extramural
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