Biosynthesis of the Novel Endogenous 15-Lipoxygenase Metabolites <i>N</i>-13-Hydroxy-octodecadienoyl-ethanolamine and 13-Hydroxy-octodecadienoyl-glycerol by Human Neutrophils and Eosinophils
The endocannabinoids 2-arachidonoyl-glycerol and <i>N</i>-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-arachidon...
| Main Authors: | , , , , , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2021-09-01
|
| Series: | Cells |
| Subjects: | |
| Online Access: | https://www.mdpi.com/2073-4409/10/9/2322 |
| _version_ | 1797519885126860800 |
|---|---|
| author | Anne-Sophie Archambault Francesco Tinto Élizabeth Dumais Volatiana Rakotoarivelo Magdalena Kostrzewa Pier-Luc Plante Cyril Martin Mélissa Simard Cristoforo Silvestri Roxane Pouliot Michel Laviolette Louis-Philippe Boulet Rosa Maria Vitale Alessia Ligresti Vincenzo Di Marzo Nicolas Flamand |
| author_facet | Anne-Sophie Archambault Francesco Tinto Élizabeth Dumais Volatiana Rakotoarivelo Magdalena Kostrzewa Pier-Luc Plante Cyril Martin Mélissa Simard Cristoforo Silvestri Roxane Pouliot Michel Laviolette Louis-Philippe Boulet Rosa Maria Vitale Alessia Ligresti Vincenzo Di Marzo Nicolas Flamand |
| author_sort | Anne-Sophie Archambault |
| collection | DOAJ |
| description | The endocannabinoids 2-arachidonoyl-glycerol and <i>N</i>-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 <i>N</i>-arachidonoyl-ethanolamine, the endocannabinoidome also includes other monoacylglycerols and <i>N</i>-acyl-ethanolamines such as 1-linoleoyl-glycerol (1-LG) and <i>N</i>-linoleoyl-ethanolamine (LEA). By increasing monoacylglycerols and/or <i>N</i>-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 1<i>Z</i>,4<i>Z</i>-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. <i>N</i>-13-hydroxy-octodecadienoyl-ethanolamine (13-HODE-EA) and 13-hydroxy-octodecadienoyl-glycerol (13-HODE-G)<b>,</b> 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 inhibition 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. |
| first_indexed | 2024-03-10T07:49:07Z |
| format | Article |
| id | doaj.art-32ef6306d30448259f4ffcbb9d4159c1 |
| institution | Directory Open Access Journal |
| issn | 2073-4409 |
| language | English |
| last_indexed | 2024-03-10T07:49:07Z |
| publishDate | 2021-09-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cells |
| spelling | doaj.art-32ef6306d30448259f4ffcbb9d4159c12023-11-22T12:24:17ZengMDPI AGCells2073-44092021-09-01109232210.3390/cells10092322Biosynthesis of the Novel Endogenous 15-Lipoxygenase Metabolites <i>N</i>-13-Hydroxy-octodecadienoyl-ethanolamine and 13-Hydroxy-octodecadienoyl-glycerol by Human Neutrophils and EosinophilsAnne-Sophie Archambault0Francesco Tinto1Élizabeth Dumais2Volatiana Rakotoarivelo3Magdalena Kostrzewa4Pier-Luc Plante5Cyril Martin6Mélissa Simard7Cristoforo Silvestri8Roxane Pouliot9Michel Laviolette10Louis-Philippe Boulet11Rosa Maria Vitale12Alessia Ligresti13Vincenzo Di Marzo14Nicolas Flamand15Centre de Recherche de l’Institut Universitaire de Cardiologie et de Pneumologie de Québec, Faculté de Médecine, Université Laval, Québec City, QC G1V 4G5, CanadaCentre de Recherche de l’Institut Universitaire de Cardiologie et de Pneumologie de Québec, Faculté de Médecine, Université Laval, Québec City, QC G1V 4G5, CanadaCentre de Recherche de l’Institut Universitaire de Cardiologie et de Pneumologie de Québec, Faculté de Médecine, Université Laval, Québec City, QC G1V 4G5, CanadaCentre de Recherche de l’Institut Universitaire de Cardiologie et de Pneumologie de Québec, Faculté de Médecine, Université Laval, Québec City, QC G1V 4G5, CanadaEndocannabinoid Research Group, Institute of Biomolecular Chemistry, Consiglio Nazionale Delle Ricerche (CNR), 80078 Pozzuoli, ItalyInstitut sur la Nutrition et les Aliments Fonctionnels, Centre NUTRISS, École de Nutrition, Faculté des Sciences de L’agriculture et de L’alimentation, Université Laval, Québec City, QC G1V 0A6, CanadaCentre de Recherche de l’Institut Universitaire de Cardiologie et de Pneumologie de Québec, Faculté de Médecine, Université Laval, Québec City, QC G1V 4G5, CanadaCentre de Recherche de l’Institut Universitaire de Cardiologie et de Pneumologie de Québec, Faculté de Médecine, Université Laval, Québec City, QC G1V 4G5, CanadaCentre de Recherche de l’Institut Universitaire de Cardiologie et de Pneumologie de Québec, Faculté de Médecine, Université Laval, Québec City, QC G1V 4G5, CanadaFaculté de Pharmacie de l’Université Laval and Centre de Recherche en Organogénèse Expérimentale de l’Université Laval/LOEX, Axe Médecine Régénératrice, Centre de Recherche du CHU de Québec-Université Laval, Québec City, QC G1V 0A6, CanadaCentre de Recherche de l’Institut Universitaire de Cardiologie et de Pneumologie de Québec, Faculté de Médecine, Université Laval, Québec City, QC G1V 4G5, CanadaCentre de Recherche de l’Institut Universitaire de Cardiologie et de Pneumologie de Québec, Faculté de Médecine, Université Laval, Québec City, QC G1V 4G5, CanadaEndocannabinoid Research Group, Institute of Biomolecular Chemistry, Consiglio Nazionale Delle Ricerche (CNR), 80078 Pozzuoli, ItalyEndocannabinoid Research Group, Institute of Biomolecular Chemistry, Consiglio Nazionale Delle Ricerche (CNR), 80078 Pozzuoli, ItalyCentre de Recherche de l’Institut Universitaire de Cardiologie et de Pneumologie de Québec, Faculté de Médecine, Université Laval, Québec City, QC G1V 4G5, CanadaCentre de Recherche de l’Institut Universitaire de Cardiologie et de Pneumologie de Québec, Faculté de Médecine, Université Laval, Québec City, QC G1V 4G5, CanadaThe endocannabinoids 2-arachidonoyl-glycerol and <i>N</i>-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 <i>N</i>-arachidonoyl-ethanolamine, the endocannabinoidome also includes other monoacylglycerols and <i>N</i>-acyl-ethanolamines such as 1-linoleoyl-glycerol (1-LG) and <i>N</i>-linoleoyl-ethanolamine (LEA). By increasing monoacylglycerols and/or <i>N</i>-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 1<i>Z</i>,4<i>Z</i>-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. <i>N</i>-13-hydroxy-octodecadienoyl-ethanolamine (13-HODE-EA) and 13-hydroxy-octodecadienoyl-glycerol (13-HODE-G)<b>,</b> 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 inhibition 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.https://www.mdpi.com/2073-4409/10/9/2322endocannabinoidlinoleic acidlinoleoyl-glycerol13-HODE2-arachidonoyl-glycerolanandamide |
| spellingShingle | Anne-Sophie Archambault Francesco Tinto Élizabeth Dumais Volatiana Rakotoarivelo Magdalena Kostrzewa Pier-Luc Plante Cyril Martin Mélissa Simard Cristoforo Silvestri Roxane Pouliot Michel Laviolette Louis-Philippe Boulet Rosa Maria Vitale Alessia Ligresti Vincenzo Di Marzo Nicolas Flamand Biosynthesis of the Novel Endogenous 15-Lipoxygenase Metabolites <i>N</i>-13-Hydroxy-octodecadienoyl-ethanolamine and 13-Hydroxy-octodecadienoyl-glycerol by Human Neutrophils and Eosinophils Cells endocannabinoid linoleic acid linoleoyl-glycerol 13-HODE 2-arachidonoyl-glycerol anandamide |
| title | Biosynthesis of the Novel Endogenous 15-Lipoxygenase Metabolites <i>N</i>-13-Hydroxy-octodecadienoyl-ethanolamine and 13-Hydroxy-octodecadienoyl-glycerol by Human Neutrophils and Eosinophils |
| title_full | Biosynthesis of the Novel Endogenous 15-Lipoxygenase Metabolites <i>N</i>-13-Hydroxy-octodecadienoyl-ethanolamine and 13-Hydroxy-octodecadienoyl-glycerol by Human Neutrophils and Eosinophils |
| title_fullStr | Biosynthesis of the Novel Endogenous 15-Lipoxygenase Metabolites <i>N</i>-13-Hydroxy-octodecadienoyl-ethanolamine and 13-Hydroxy-octodecadienoyl-glycerol by Human Neutrophils and Eosinophils |
| title_full_unstemmed | Biosynthesis of the Novel Endogenous 15-Lipoxygenase Metabolites <i>N</i>-13-Hydroxy-octodecadienoyl-ethanolamine and 13-Hydroxy-octodecadienoyl-glycerol by Human Neutrophils and Eosinophils |
| title_short | Biosynthesis of the Novel Endogenous 15-Lipoxygenase Metabolites <i>N</i>-13-Hydroxy-octodecadienoyl-ethanolamine and 13-Hydroxy-octodecadienoyl-glycerol by Human Neutrophils and Eosinophils |
| title_sort | biosynthesis of the novel endogenous 15 lipoxygenase metabolites i n i 13 hydroxy octodecadienoyl ethanolamine and 13 hydroxy octodecadienoyl glycerol by human neutrophils and eosinophils |
| topic | endocannabinoid linoleic acid linoleoyl-glycerol 13-HODE 2-arachidonoyl-glycerol anandamide |
| url | https://www.mdpi.com/2073-4409/10/9/2322 |
| work_keys_str_mv | AT annesophiearchambault biosynthesisofthenovelendogenous15lipoxygenasemetabolitesini13hydroxyoctodecadienoylethanolamineand13hydroxyoctodecadienoylglycerolbyhumanneutrophilsandeosinophils AT francescotinto biosynthesisofthenovelendogenous15lipoxygenasemetabolitesini13hydroxyoctodecadienoylethanolamineand13hydroxyoctodecadienoylglycerolbyhumanneutrophilsandeosinophils AT elizabethdumais biosynthesisofthenovelendogenous15lipoxygenasemetabolitesini13hydroxyoctodecadienoylethanolamineand13hydroxyoctodecadienoylglycerolbyhumanneutrophilsandeosinophils AT volatianarakotoarivelo biosynthesisofthenovelendogenous15lipoxygenasemetabolitesini13hydroxyoctodecadienoylethanolamineand13hydroxyoctodecadienoylglycerolbyhumanneutrophilsandeosinophils AT magdalenakostrzewa biosynthesisofthenovelendogenous15lipoxygenasemetabolitesini13hydroxyoctodecadienoylethanolamineand13hydroxyoctodecadienoylglycerolbyhumanneutrophilsandeosinophils AT pierlucplante biosynthesisofthenovelendogenous15lipoxygenasemetabolitesini13hydroxyoctodecadienoylethanolamineand13hydroxyoctodecadienoylglycerolbyhumanneutrophilsandeosinophils AT cyrilmartin biosynthesisofthenovelendogenous15lipoxygenasemetabolitesini13hydroxyoctodecadienoylethanolamineand13hydroxyoctodecadienoylglycerolbyhumanneutrophilsandeosinophils AT melissasimard biosynthesisofthenovelendogenous15lipoxygenasemetabolitesini13hydroxyoctodecadienoylethanolamineand13hydroxyoctodecadienoylglycerolbyhumanneutrophilsandeosinophils AT cristoforosilvestri biosynthesisofthenovelendogenous15lipoxygenasemetabolitesini13hydroxyoctodecadienoylethanolamineand13hydroxyoctodecadienoylglycerolbyhumanneutrophilsandeosinophils AT roxanepouliot biosynthesisofthenovelendogenous15lipoxygenasemetabolitesini13hydroxyoctodecadienoylethanolamineand13hydroxyoctodecadienoylglycerolbyhumanneutrophilsandeosinophils AT michellaviolette biosynthesisofthenovelendogenous15lipoxygenasemetabolitesini13hydroxyoctodecadienoylethanolamineand13hydroxyoctodecadienoylglycerolbyhumanneutrophilsandeosinophils AT louisphilippeboulet biosynthesisofthenovelendogenous15lipoxygenasemetabolitesini13hydroxyoctodecadienoylethanolamineand13hydroxyoctodecadienoylglycerolbyhumanneutrophilsandeosinophils AT rosamariavitale biosynthesisofthenovelendogenous15lipoxygenasemetabolitesini13hydroxyoctodecadienoylethanolamineand13hydroxyoctodecadienoylglycerolbyhumanneutrophilsandeosinophils AT alessialigresti biosynthesisofthenovelendogenous15lipoxygenasemetabolitesini13hydroxyoctodecadienoylethanolamineand13hydroxyoctodecadienoylglycerolbyhumanneutrophilsandeosinophils AT vincenzodimarzo biosynthesisofthenovelendogenous15lipoxygenasemetabolitesini13hydroxyoctodecadienoylethanolamineand13hydroxyoctodecadienoylglycerolbyhumanneutrophilsandeosinophils AT nicolasflamand biosynthesisofthenovelendogenous15lipoxygenasemetabolitesini13hydroxyoctodecadienoylethanolamineand13hydroxyoctodecadienoylglycerolbyhumanneutrophilsandeosinophils |