Document Detail

Identification and absolute configuration of dihydroxy-arachidonic acids formed by oxygenation of 5S-HETE by native and aspirin-acetylated COX-2.
MedLine Citation:
PMID:  19752399     Owner:  NLM     Status:  MEDLINE    
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.
Surafel Mulugeta; Takashi Suzuki; Noemi Tejera Hernandez; Markus Griesser; William E Boeglin; Claus Schneider
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Publication Detail:
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:
Title:  Journal of lipid research     Volume:  51     ISSN:  0022-2275     ISO Abbreviation:  J. Lipid Res.     Publication Date:  2010 Mar 
Date Detail:
Created Date:  2010-02-16     Completed Date:  2010-05-07     Revised Date:  2014-09-17    
Medline Journal Info:
Nlm Unique ID:  0376606     Medline TA:  J Lipid Res     Country:  United States    
Other Details:
Languages:  eng     Pagination:  575-85     Citation Subset:  IM    
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MeSH Terms
Acetylation / drug effects
Aspirin / chemistry,  pharmacology*
Cell Line
Circular Dichroism
Cyclooxygenase 2 / chemistry,  metabolism*
Hydroxyeicosatetraenoic Acids / analysis,  biosynthesis,  chemistry*,  metabolism*
Oxygen / metabolism*
Grant Support
Reg. No./Substance:
0/Hydroxyeicosatetraenoic Acids; EC 2; R16CO5Y76E/Aspirin; S88TT14065/Oxygen

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

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