Biosynthesis of the Novel Endogenous 15-Lipoxygenase Metabolites N-13-Hydroxy-octodecadienoyl-ethanolamine and 13-Hydroxy-octodecadienoyl-glycerol by Human Neutrophils and Eosinophils
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 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.
| Medienart: |
E-Artikel |
|---|
| Erscheinungsjahr: |
2021 |
|---|---|
| Erschienen: |
2021 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:10 |
|---|---|
| Enthalten in: |
Cells - 10(2021), 9 vom: 05. Sept. |
| Sprache: |
Englisch |
|---|
| Beteiligte Personen: |
Archambault, Anne-Sophie [VerfasserIn] |
|---|
| Links: |
|---|
| Anmerkungen: |
Date Completed 16.11.2021 Date Revised 03.04.2024 published: Electronic Citation Status MEDLINE |
|---|
| doi: |
10.3390/cells10092322 |
|---|
| funding: |
|
|---|---|
| Förderinstitution / Projekttitel: |
|
| PPN (Katalog-ID): |
NLM331135795 |
|---|
| LEADER | 01000caa a22002652 4500 | ||
|---|---|---|---|
| 001 | NLM331135795 | ||
| 003 | DE-627 | ||
| 005 | 20240403233743.0 | ||
| 007 | cr uuu---uuuuu | ||
| 008 | 231225s2021 xx |||||o 00| ||eng c | ||
| 024 | 7 | |a 10.3390/cells10092322 |2 doi | |
| 028 | 5 | 2 | |a pubmed24n1362.xml |
| 035 | |a (DE-627)NLM331135795 | ||
| 035 | |a (NLM)34571971 | ||
| 035 | |a (PII)2322 | ||
| 040 | |a DE-627 |b ger |c DE-627 |e rakwb | ||
| 041 | |a eng | ||
| 100 | 1 | |a Archambault, Anne-Sophie |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Biosynthesis of the Novel Endogenous 15-Lipoxygenase Metabolites N-13-Hydroxy-octodecadienoyl-ethanolamine and 13-Hydroxy-octodecadienoyl-glycerol by Human Neutrophils and Eosinophils |
| 264 | 1 | |c 2021 | |
| 336 | |a Text |b txt |2 rdacontent | ||
| 337 | |a ƒaComputermedien |b c |2 rdamedia | ||
| 338 | |a ƒa Online-Ressource |b cr |2 rdacarrier | ||
| 500 | |a Date Completed 16.11.2021 | ||
| 500 | |a Date Revised 03.04.2024 | ||
| 500 | |a published: Electronic | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a 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 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 | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Research Support, Non-U.S. Gov't | |
| 650 | 4 | |a 13-HODE | |
| 650 | 4 | |a 2-arachidonoyl-glycerol | |
| 650 | 4 | |a N-linoleoyl-ethanolamine | |
| 650 | 4 | |a anandamide | |
| 650 | 4 | |a eicosanoid | |
| 650 | 4 | |a endocannabinoid | |
| 650 | 4 | |a eosinophils | |
| 650 | 4 | |a linoleic acid | |
| 650 | 4 | |a linoleoyl-glycerol | |
| 650 | 4 | |a neutrophils | |
| 650 | 7 | |a Linoleic Acids |2 NLM | |
| 650 | 7 | |a Peroxisome Proliferator-Activated Receptors |2 NLM | |
| 650 | 7 | |a Receptors, Cannabinoid |2 NLM | |
| 650 | 7 | |a TRPV Cation Channels |2 NLM | |
| 650 | 7 | |a TRPV1 protein, human |2 NLM | |
| 650 | 7 | |a Arachidonate 15-Lipoxygenase |2 NLM | |
| 650 | 7 | |a EC 1.13.11.33 |2 NLM | |
| 700 | 1 | |a Tinto, Francesco |e verfasserin |4 aut | |
| 700 | 1 | |a Dumais, Élizabeth |e verfasserin |4 aut | |
| 700 | 1 | |a Rakotoarivelo, Volatiana |e verfasserin |4 aut | |
| 700 | 1 | |a Kostrzewa, Magdalena |e verfasserin |4 aut | |
| 700 | 1 | |a Plante, Pier-Luc |e verfasserin |4 aut | |
| 700 | 1 | |a Martin, Cyril |e verfasserin |4 aut | |
| 700 | 1 | |a Simard, Mélissa |e verfasserin |4 aut | |
| 700 | 1 | |a Silvestri, Cristoforo |e verfasserin |4 aut | |
| 700 | 1 | |a Pouliot, Roxane |e verfasserin |4 aut | |
| 700 | 1 | |a Laviolette, Michel |e verfasserin |4 aut | |
| 700 | 1 | |a Boulet, Louis-Philippe |e verfasserin |4 aut | |
| 700 | 1 | |a Vitale, Rosa Maria |e verfasserin |4 aut | |
| 700 | 1 | |a Ligresti, Alessia |e verfasserin |4 aut | |
| 700 | 1 | |a Di Marzo, Vincenzo |e verfasserin |4 aut | |
| 700 | 1 | |a Flamand, Nicolas |e verfasserin |4 aut | |
| 773 | 0 | 8 | |i Enthalten in |t Cells |d 2011 |g 10(2021), 9 vom: 05. Sept. |w (DE-627)NLM227066421 |x 2073-4409 |7 nnns |
| 773 | 1 | 8 | |g volume:10 |g year:2021 |g number:9 |g day:05 |g month:09 |
| 856 | 4 | 0 | |u http://dx.doi.org/10.3390/cells10092322 |3 Volltext |
| 912 | |a GBV_USEFLAG_A | ||
| 912 | |a GBV_NLM | ||
| 951 | |a AR | ||
| 952 | |d 10 |j 2021 |e 9 |b 05 |c 09 | ||