Involvement of the γ Isoform of cPLA<sub>2</sub> in the Biosynthesis of Bioactive <i>N-</i>Acylethanolamines
Arachidonylethanolamide (anandamide) acts as an endogenous ligand of cannabinoid receptors, while other <i>N-</i>acylethanolamines (NAEs), such as palmitylethanolamide and oleylethanolamide, show analgesic, anti-inflammatory, and appetite-suppressing effects through other receptors. In m...
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MDPI AG
2021-08-01
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| author | Yiman Guo Toru Uyama S. M. Khaledur Rahman Mohammad Mamun Sikder Zahir Hussain Kazuhito Tsuboi Minoru Miyake Natsuo Ueda |
| author_facet | Yiman Guo Toru Uyama S. M. Khaledur Rahman Mohammad Mamun Sikder Zahir Hussain Kazuhito Tsuboi Minoru Miyake Natsuo Ueda |
| author_sort | Yiman Guo |
| collection | DOAJ |
| description | Arachidonylethanolamide (anandamide) acts as an endogenous ligand of cannabinoid receptors, while other <i>N-</i>acylethanolamines (NAEs), such as palmitylethanolamide and oleylethanolamide, show analgesic, anti-inflammatory, and appetite-suppressing effects through other receptors. In mammalian tissues, NAEs, including anandamide, are produced from glycerophospholipid via <i>N-</i>acyl-phosphatidylethanolamine (NAPE). The ɛ isoform of cytosolic phospholipase A<sub>2</sub> (cPLA<sub>2</sub>) functions as an <i>N-</i>acyltransferase to form NAPE. Since the cPLA<sub>2</sub> family consists of six isoforms (α, β, γ, δ, ɛ, and ζ), the present study investigated a possible involvement of isoforms other than ɛ in the NAE biosynthesis. Firstly, when the cells overexpressing one of the cPLA<sub>2</sub> isoforms were labeled with [<sup>14</sup>C]ethanolamine, the increase in the production of [<sup>14</sup>C]NAPE was observed only with the ɛ-expressing cells. Secondly, when the cells co-expressing ɛ and one of the other isoforms were analyzed, the increase in [<sup>14</sup>C]<i>N</i>-acyl-lysophosphatidylethanolamine (lysoNAPE) and [<sup>14</sup>C]NAE was seen with the combination of ɛ and γ isoforms. Furthermore, the purified cPLA<sub>2</sub>γ hydrolyzed not only NAPE to lysoNAPE, but also lysoNAPE to glycerophospho-<i>N</i>-acylethanolamine (GP-NAE). Thus, the produced GP-NAE was further hydrolyzed to NAE by glycerophosphodiesterase 1. These results suggested that cPLA<sub>2</sub>γ is involved in the biosynthesis of NAE by its phospholipase A<sub>1</sub>/A<sub>2</sub> and lysophospholipase activities. |
| first_indexed | 2024-03-10T08:07:02Z |
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| institution | Directory Open Access Journal |
| issn | 1420-3049 |
| language | English |
| last_indexed | 2024-03-10T08:07:02Z |
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| spelling | doaj.art-965937f7660345debe049af4d01ec9e02023-11-22T11:00:47ZengMDPI AGMolecules1420-30492021-08-012617521310.3390/molecules26175213Involvement of the γ Isoform of cPLA<sub>2</sub> in the Biosynthesis of Bioactive <i>N-</i>AcylethanolaminesYiman Guo0Toru Uyama1S. M. Khaledur Rahman2Mohammad Mamun Sikder3Zahir Hussain4Kazuhito Tsuboi5Minoru Miyake6Natsuo Ueda7Department of Biochemistry, Kagawa University School of Medicine, 1750-1 Ikenobe, Miki, Kagawa 761-0793, JapanDepartment of Biochemistry, Kagawa University School of Medicine, 1750-1 Ikenobe, Miki, Kagawa 761-0793, JapanDepartment of Biochemistry, Kagawa University School of Medicine, 1750-1 Ikenobe, Miki, Kagawa 761-0793, JapanDepartment of Biochemistry, Kagawa University School of Medicine, 1750-1 Ikenobe, Miki, Kagawa 761-0793, JapanDepartment of Biochemistry, Kagawa University School of Medicine, 1750-1 Ikenobe, Miki, Kagawa 761-0793, JapanDepartment of Pharmacology, Kawasaki Medical School, 577 Matsushima, Kurashiki, Okayama 701-0192, JapanDepartment of Oral and Maxillofacial Surgery, Kagawa University School of Medicine, 1750-1 Ikenobe, Miki, Kagawa 761-0793, JapanDepartment of Biochemistry, Kagawa University School of Medicine, 1750-1 Ikenobe, Miki, Kagawa 761-0793, JapanArachidonylethanolamide (anandamide) acts as an endogenous ligand of cannabinoid receptors, while other <i>N-</i>acylethanolamines (NAEs), such as palmitylethanolamide and oleylethanolamide, show analgesic, anti-inflammatory, and appetite-suppressing effects through other receptors. In mammalian tissues, NAEs, including anandamide, are produced from glycerophospholipid via <i>N-</i>acyl-phosphatidylethanolamine (NAPE). The ɛ isoform of cytosolic phospholipase A<sub>2</sub> (cPLA<sub>2</sub>) functions as an <i>N-</i>acyltransferase to form NAPE. Since the cPLA<sub>2</sub> family consists of six isoforms (α, β, γ, δ, ɛ, and ζ), the present study investigated a possible involvement of isoforms other than ɛ in the NAE biosynthesis. Firstly, when the cells overexpressing one of the cPLA<sub>2</sub> isoforms were labeled with [<sup>14</sup>C]ethanolamine, the increase in the production of [<sup>14</sup>C]NAPE was observed only with the ɛ-expressing cells. Secondly, when the cells co-expressing ɛ and one of the other isoforms were analyzed, the increase in [<sup>14</sup>C]<i>N</i>-acyl-lysophosphatidylethanolamine (lysoNAPE) and [<sup>14</sup>C]NAE was seen with the combination of ɛ and γ isoforms. Furthermore, the purified cPLA<sub>2</sub>γ hydrolyzed not only NAPE to lysoNAPE, but also lysoNAPE to glycerophospho-<i>N</i>-acylethanolamine (GP-NAE). Thus, the produced GP-NAE was further hydrolyzed to NAE by glycerophosphodiesterase 1. These results suggested that cPLA<sub>2</sub>γ is involved in the biosynthesis of NAE by its phospholipase A<sub>1</sub>/A<sub>2</sub> and lysophospholipase activities.https://www.mdpi.com/1420-3049/26/17/5213<i>N-</i>acyltransferaseanandamideendocannabinoidphospholipase A<sub>2</sub> |
| spellingShingle | Yiman Guo Toru Uyama S. M. Khaledur Rahman Mohammad Mamun Sikder Zahir Hussain Kazuhito Tsuboi Minoru Miyake Natsuo Ueda Involvement of the γ Isoform of cPLA<sub>2</sub> in the Biosynthesis of Bioactive <i>N-</i>Acylethanolamines Molecules <i>N-</i>acyltransferase anandamide endocannabinoid phospholipase A<sub>2</sub> |
| title | Involvement of the γ Isoform of cPLA<sub>2</sub> in the Biosynthesis of Bioactive <i>N-</i>Acylethanolamines |
| title_full | Involvement of the γ Isoform of cPLA<sub>2</sub> in the Biosynthesis of Bioactive <i>N-</i>Acylethanolamines |
| title_fullStr | Involvement of the γ Isoform of cPLA<sub>2</sub> in the Biosynthesis of Bioactive <i>N-</i>Acylethanolamines |
| title_full_unstemmed | Involvement of the γ Isoform of cPLA<sub>2</sub> in the Biosynthesis of Bioactive <i>N-</i>Acylethanolamines |
| title_short | Involvement of the γ Isoform of cPLA<sub>2</sub> in the Biosynthesis of Bioactive <i>N-</i>Acylethanolamines |
| title_sort | involvement of the γ isoform of cpla sub 2 sub in the biosynthesis of bioactive i n i acylethanolamines |
| topic | <i>N-</i>acyltransferase anandamide endocannabinoid phospholipase A<sub>2</sub> |
| url | https://www.mdpi.com/1420-3049/26/17/5213 |
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