Biosynthesis of the Novel Endogenous 15-Lipoxygenase Metabolites N-13-Hydroxy-octodecadienoyl-ethanolamine and 13-Hydroxy-octodecadienoyl-glycerol by Human Neutrophils and Eosinophils
| Autor: | Mélissa Simard, Roxane Pouliot, Rosa Maria Vitale, Michel Laviolette, Pier-Luc Plante, Nicolas Flamand, Cyril Martin, Alessia Ligresti, Cristoforo Silvestri, Volatiana Rakotoarivelo, Anne-Sophie Archambault, Magdalena Kostrzewa, Louis-Philippe Boulet, Francesco Tinto, Élizabeth Dumais, Vincenzo Di Marzo |
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| Jazyk: | angličtina |
| Předmět: |
linoleic acid
PPARs QH301-705.5 Linoleic acid Endogeny chemistry.chemical_compound Lipoxygenase Ethanolamine cannabinoid receptors Biosynthesis neutrophils anandamide linoleoyl-glycerol Biology (General) 2-arachidonoyl-glycerol biology General Medicine Anandamide endocannabinoid 13-HODE Endocannabinoid system chemistry Biochemistry Eicosanoid eicosanoid biology.protein lipids (amino acids peptides and proteins) eosinophils |
| Zdroj: | Cells, Vol 10, Iss 2322, p 2322 (2021) Cells Volume 10 Issue 9 Cells 10 (2021). doi:10.3390/cells10092322 info:cnr-pdr/source/autori:Archambault A.-S.; Tinto F.; Dumais E.; Rakotoarivelo V.; Kostrzewa M.; Plante P.-L.; Martin C.; Simard M.; Silvestri C.; Pouliot R.; Laviolette M.; Boulet L.-P.; Vitale R.M.; Ligresti A.; Di Marzo V.; Flamand N./titolo:Biosynthesis of the novel endogenous 15-lipoxygenase metabolites N-13-hydroxy-octodecadienoyl-ethanolamine and 13-hydroxy-octodecadienoyl-glycerol by human neutrophils and Eosinophils/doi:10.3390%2Fcells10092322/rivista:Cells/anno:2021/pagina_da:/pagina_a:/intervallo_pagine:/volume:10 |
| ISSN: | 2073-4409 |
| DOI: | 10.3390/cells10092322 |
| Popis: | The endocannabinoids 2-arachidonoyl-glycerol and N-arachidonoyl-ethanolamine are lipids regulating many physiological processes, notably inflammation. Endocannabinoid hydrolysis inhibitors are now being investigated as potential anti-inflammatory agents. In addition to 2-arachidonoyl-glycerol and N-arachidonoyl-ethanolamine, the endocannabinoidome also includes other monoacylglycerols and N-acyl-ethanolamines such as 1-linoleoyl-glycerol (1-LG) and N-linoleoyl-ethanolamine (LEA). By increasing monoacylglycerols and/or N-acyl-ethanolamine levels, endocannabinoid hydrolysis inhibitors will likely increase the levels of their metabolites. Herein, we investigated whether 1-LG and LEA were substrates for the 15-lipoxygenase pathway, given that both possess a 1Z,4Z-pentadiene motif, near their omega end. We thus assessed how human eosinophils and neutrophils biosynthesized the 15-lipoxygenase metabolites of 1-LG and LEA. Linoleic acid (LA), a well-documented substrate of 15-lipoxygenases, was used as positive control. N-13-hydroxy-octodecadienoyl-ethanolamine (13-HODE-EA) and 13-hydroxy-octodecadienoyl-glycerol (13-HODE-G), the 15-lipoxygenase metabolites of LEA and 1-LG, were synthesized using Novozym 435 and soybean lipoxygenase. Eosinophils, which express the 15-lipoxygenase-1, metabolized LA, 1-LG, and LEA into their 13-hydroxy derivatives. This was almost complete after five minutes. Substrate preference of eosinophils was LA > LEA > 1-LG in presence of 13-HODE-G hydrolysis with methyl-arachidonoyl-fluorophosphonate. Human neutrophils also metabolized LA, 1-LG, and LEA into their 13-hydroxy derivatives. This was maximal after 15–30 s. Substrate preference was LA ≫ 1-LG > LEA. Importantly, 13-HODE-G was found in humans and mouse tissue samples. In conclusion, our data show that human eosinophils and neutrophils metabolize 1-LG and LEA into the novel endogenous 15-lipoxygenase metabolites 13-HODE-G and 13-HODE-EA. The full biological importance of 13-HODE-G and 13-HODE-EA remains to be explored. |
| Databáze: | OpenAIRE |
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