Novel COX-2 products of n-3 polyunsaturated fatty acid-ethanolamine-conjugates identified in RAW264.7 macrophages

Autor: Bauke Albada, Han Zuilhof, Renger F. Witkamp, Michiel G.J. Balvers, Ian de Bus
Jazyk: angličtina
Rok vydání: 2019
Předmět:
Lipopolysaccharides
0301 basic medicine
030204 cardiovascular system & hematology
Biochemistry
law.invention
prostaglandins
Mice
chemistry.chemical_compound
0302 clinical medicine
Endocrinology
law
Ethanolamine
cyclooxygenase 2
Beta oxidation
Research Articles
fatty acid oxidation
mass spectrometry
chemistry.chemical_classification
biology
Anandamide
Organische Chemie
Recombinant Proteins
Nutritional Biology
cyclooxygenase
Recombinant DNA
lipids (amino acids
peptides
and proteins)
medicine.symptom
Polyunsaturated fatty acid
Cell Survival
fatty acid amides
Inflammation
QD415-436
03 medical and health sciences
Fatty Acids
Omega-3
medicine
Animals
high-performance liquid chromatography
HNRU&LB
VLAG
Macrophages
Organic Chemistry
Cell Biology
RAW 264.7 Cells
030104 developmental biology
Enzyme
chemistry
inflammation
biology.protein
Cyclooxygenase
Chromatography
Liquid
Zdroj: Journal of Lipid Research, Vol 60, Iss 11, Pp 1829-1840 (2019)
Journal of Lipid Research
Journal of Lipid Research 60 (2019) 11
Journal of Lipid Research, 60(11), 1829-1840
ISSN: 0022-2275
Popis: Cyclooxygenase 2 (COX-2) plays a key role in the regulation of inflammation by catalyzing the oxygenation of PUFAs to prostaglandins (PGs) and hydroperoxides. Next to this, COX-2 can metabolize neutral lipids, including endocannabinoid-like esters and amides. We developed an LC-HRMS-based human recombinant (h)COX-2 screening assay to examine its ability to also convert n-3 PUFA-derived N-acylethanolamines. Our assay yields known hCOX-2-derived products from established PUFAs and anandamide. Subsequently, we proved that eicosapentaenoylethanolamide (EPEA), the N-acylethanolamine derivative of EPA, is converted into PGE3-ethanolamide (PGE3-EA), and into 11-, 14-, and 18-hydroxyeicosapentaenoyl-EA (11-, 14-, and 18-HEPE-EA, respectively). Interestingly, we demonstrated that docosahexaenoylethanolamide (DHEA) is converted by hCOX-2 into the previously unknown metabolites, 13- and 16-hydroxy-DHEA (13- and 16-HDHEA, respectively). These products were also produced by lipopolysaccharide-stimulated RAW267.4 macrophages incubated with DHEA. No oxygenated DHEA metabolites were detected when the selective COX-2 inhibitor, celecoxib, was added to the cells, further underlining the role of COX-2 in the formation of the novel hydroxylated products. This work demonstrates for the first time that DHEA and EPEA are converted by COX-2 into previously unknown hydroxylated metabolites and invites future studies toward the biological effects of these metabolites.
Databáze: OpenAIRE
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