| Identification and absolute configuration of dihydroxy-arachidonic acids formed by oxygenation of 5S-HETE by native and aspirin-acetylated COX-2. | |
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MedLine Citation:
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PMID: 19752399 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Biosynthesis of the prostaglandin endoperoxide by the cyclooxygenase (COX) enzymes is accompanied by formation of a small amount of 11R-hydroxyeicosatetraenoic acid (HETE), 15R-HETE, and 15S-HETE as by-products. Acetylation of COX-2 by aspirin abrogates prostaglandin synthesis and triggers formation of 15R-HETE as the sole product of oxygenation of arachidonic acid. Here, we investigated the formation of by-products of the transformation of 5S-HETE by native COX-2 and by aspirin-acetylated COX-2 using HPLC-ultraviolet, GC-MS, and LC-MS analysis. 5S,15S- dihydroxy (di)HETE, 5S,15R-diHETE, and 5S,11R-diHETE were identified as by-products of native COX-2, in addition to the previously described di-endoperoxide (5S,15S-dihydroxy-9S,11R,8S,12S-diperoxy-6E,13E-eicosadienoic acid) as the major oxygenation product. 5S,15R-diHETE was the only product formed by aspirin-acetylated COX-2. Both 5,15-diHETE and 5,11-diHETE were detected in CT26 mouse colon carcinoma cells as well as in lipopolysaccharide-activated RAW264.7 cells incubated with 5S-HETE, and their formation was attenuated in the presence of the COX-2 specific inhibitor, NS-398. Aspirin-treated CT26 cells gave 5,15-diHETE as the most prominent product formed from 5S-HETE. 5S,15S-diHETE has been described as a product of the cross-over of 5-lipoxygenase (5-LOX) and 15-LOX activities in elicited rat mononuclear cells and human leukocytes, and our studies implicate cross-over of the 5-LOX and COX-2 pathways as an additional biosynthetic route. |
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Authors:
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Surafel Mulugeta; Takashi Suzuki; Noemi Tejera Hernandez; Markus Griesser; William E Boeglin; Claus Schneider |
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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; Research Support, U.S. Gov't, Non-P.H.S. Date: 2009-09-14 |
Journal Detail:
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Title: Journal of lipid research Volume: 51 ISSN: 0022-2275 ISO Abbreviation: J. Lipid Res. Publication Date: 2010 Mar |
Date Detail:
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Created Date: 2010-02-16 Completed Date: 2010-05-07 Revised Date: 2011-07-25 |
Medline Journal Info:
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Nlm Unique ID: 0376606 Medline TA: J Lipid Res Country: United States |
Other Details:
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Languages: eng Pagination: 575-85 Citation Subset: IM |
Affiliation:
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Division of Clinical Pharmacology, Department of Pharmacology, Vanderbilt University Medical School, Nashville, TN 37232, USA. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Acetylation
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drug effects Animals Aspirin / chemistry, pharmacology* Cell Line Circular Dichroism Cyclooxygenase 2 / chemistry, metabolism* Humans Hydroxyeicosatetraenoic Acids / analysis, biosynthesis, chemistry*, metabolism* Mice Oxygen / metabolism* Stereoisomerism |
| Grant Support | |
ID/Acronym/Agency:
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R01 GM076592-02/GM/NIGMS NIH HHS; R01GM076592/GM/NIGMS NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Hydroxyeicosatetraenoic Acids; 50-78-2/Aspirin; 7782-44-7/Oxygen; EC 1.14.99.1/Cyclooxygenase 2 |
| Comments/Corrections | |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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