| Effect of cyclooxygenase genotype and dietary fish oil on colonic eicosanoids in mice. | |
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MedLine Citation:
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PMID: 21937210 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Dietary ω3 fatty acids can modulate substrate availability for cyclooxygenases (COXs) and lipoxygenases, thus modulating downstream eicosanoid formation. This could be an alternative approach to using nonsteroidal anti-inflammatory drugs and other COX inhibitors for limiting Prostaglandin E(2) (PGE(2)) synthesis in colon cancer prevention. The aims of this study were to evaluate to what extent COX- and lipoxygenase-derived products could be modulated by dietary fish oil in normal colonic mucosa and to evaluate the role of COX-1 and COX-2 in the formation of these products. Mice (wild-type, COX-1 null or COX-2 null) were fed a diet supplying a broad mixture of fatty acids present in European/American diets, supplemented with either olive oil (oleate control diet) or menhaden (fish) oil ad libitum for 9-11 weeks. Colonic eicosanoid levels were measured by liquid chromatography tandem mass spectroscopy (LC-MS/MS), and proliferation was assessed by Ki67 immunohistochemistry. For the dietary alteration of colonic arachidonic acid: eicosapentaenoic ratios resulted in large shifts in formation of COX and lipoxygenase metabolites. COX-1 knockout virtually abolished PGE(2) formation, but interestingly, 12-hydroxyeicosatetraenoic (12-HETE) acid and 15-HETE formation was increased. The large changes in eicosanoid profiles were accompanied by relatively small changes in colonic crypt proliferation, but such changes in eicosanoid formation might have greater biological impact upon carcinogen challenge. These results indicate that in normal colon, inhibition of COX-2 would have little effect on reducing PGE(2) levels. |
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Authors:
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Andrew P Neilson; Zora Djuric; Jianwei Ren; Yu H Hong; Ananda Sen; Corey Lager; Yan Jiang; Shony Reuven; William L Smith; Dean E Brenner |
Publication Detail:
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Type: Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't Date: 2011-09-19 |
Journal Detail:
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Title: The Journal of nutritional biochemistry Volume: 23 ISSN: 1873-4847 ISO Abbreviation: J. Nutr. Biochem. Publication Date: 2012 Aug |
Date Detail:
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Created Date: 2012-07-23 Completed Date: 2012-12-07 Revised Date: 2013-04-16 |
Medline Journal Info:
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Nlm Unique ID: 9010081 Medline TA: J Nutr Biochem Country: United States |
Other Details:
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Languages: eng Pagination: 966-76 Citation Subset: IM |
Copyright Information:
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Copyright © 2012 Elsevier Inc. All rights reserved. |
Affiliation:
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Department of Family Medicine, University of Michigan Medical School, University of Michigan, Ann Arbor, MI 48109, USA. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Animals Cell Proliferation Colon / metabolism* Cyclooxygenase 1 / genetics*, metabolism Cyclooxygenase 2 / genetics*, metabolism Dietary Fats, Unsaturated / administration & dosage*, pharmacology Eicosanoids / metabolism* Female Fish Oils / administration & dosage*, pharmacology Genotype Hydroxyeicosatetraenoic Acids / metabolism Membrane Proteins / genetics*, metabolism Mice Mice, Inbred Strains |
| Grant Support | |
ID/Acronym/Agency:
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5T32CA009676-18/CA/NCI NIH HHS; GM 48864/GM/NIGMS NIH HHS; P30 CA046592-23/CA/NCI NIH HHS; P30-CA46592/CA/NCI NIH HHS; R01 CA120381/CA/NCI NIH HHS; R01 CA120381-05/CA/NCI NIH HHS; R01 GM068848/GM/NIGMS NIH HHS; R01 GM068848-09/GM/NIGMS NIH HHS; R01 GM68848/GM/NIGMS NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Dietary Fats, Unsaturated; 0/Eicosanoids; 0/Fish Oils; 0/Hydroxyeicosatetraenoic Acids; 0/Membrane Proteins; 73945-47-8/15-hydroxy-5,8,11,13-eicosatetraenoic acid; EC 1.14.99.-/Ptgs2 protein, mouse; EC 1.14.99.1/Cyclooxygenase 1; EC 1.14.99.1/Cyclooxygenase 2; EC 1.14.99.1/Ptgs1 protein, mouse |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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