{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,22]],"date-time":"2026-09-22T14:34:14Z","timestamp":1790087654145,"version":"4.0.1"},"reference-count":24,"publisher":"MDPI AG","issue":"17","license":[{"start":{"date-parts":[[2021,8,27]],"date-time":"2021-08-27T00:00:00Z","timestamp":1630022400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001691","name":"Japan Society for the Promotion of Science","doi-asserted-by":"publisher","award":["18K06915, 19K23828, 19K07353"],"award-info":[{"award-number":["18K06915, 19K23828, 19K07353"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecules"],"abstract":"<jats:p>Arachidonylethanolamide (anandamide) acts as an endogenous ligand of cannabinoid receptors, while other N-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 N-acyl-phosphatidylethanolamine (NAPE). The \u025b isoform of cytosolic phospholipase A2 (cPLA2) functions as an N-acyltransferase to form NAPE. Since the cPLA2 family consists of six isoforms (\u03b1, \u03b2, \u03b3, \u03b4, \u025b, and \u03b6), the present study investigated a possible involvement of isoforms other than \u025b in the NAE biosynthesis. Firstly, when the cells overexpressing one of the cPLA2 isoforms were labeled with [14C]ethanolamine, the increase in the production of [14C]NAPE was observed only with the \u025b-expressing cells. Secondly, when the cells co-expressing \u025b and one of the other isoforms were analyzed, the increase in [14C]N-acyl-lysophosphatidylethanolamine (lysoNAPE) and [14C]NAE was seen with the combination of \u025b and \u03b3 isoforms. Furthermore, the purified cPLA2\u03b3 hydrolyzed not only NAPE to lysoNAPE, but also lysoNAPE to glycerophospho-N-acylethanolamine (GP-NAE). Thus, the produced GP-NAE was further hydrolyzed to NAE by glycerophosphodiesterase 1. These results suggested that cPLA2\u03b3 is involved in the biosynthesis of NAE by its phospholipase A1\/A2 and lysophospholipase activities.<\/jats:p>","DOI":"10.3390\/molecules26175213","type":"journal-article","created":{"date-parts":[[2021,8,31]],"date-time":"2021-08-31T04:07:28Z","timestamp":1630382848000},"page":"5213","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":15,"title":["Involvement of the \u03b3 Isoform of cPLA2 in the Biosynthesis of Bioactive N-Acylethanolamines"],"prefix":"10.3390","volume":"26","author":[{"given":"Yiman","family":"Guo","sequence":"first","affiliation":[{"name":"Department of Biochemistry, Kagawa University School of Medicine, 1750-1 Ikenobe, Miki, Kagawa 761-0793, Japan"},{"name":"Department of Oral and Maxillofacial Surgery, Kagawa University School of Medicine, 1750-1 Ikenobe, Miki, Kagawa 761-0793, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Toru","family":"Uyama","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, Kagawa University School of Medicine, 1750-1 Ikenobe, Miki, Kagawa 761-0793, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0198-2582","authenticated-orcid":false,"given":"S. M. Khaledur","family":"Rahman","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, Kagawa University School of Medicine, 1750-1 Ikenobe, Miki, Kagawa 761-0793, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mohammad Mamun","family":"Sikder","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, Kagawa University School of Medicine, 1750-1 Ikenobe, Miki, Kagawa 761-0793, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zahir","family":"Hussain","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, Kagawa University School of Medicine, 1750-1 Ikenobe, Miki, Kagawa 761-0793, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kazuhito","family":"Tsuboi","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Kawasaki Medical School, 577 Matsushima, Kurashiki, Okayama 701-0192, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Minoru","family":"Miyake","sequence":"additional","affiliation":[{"name":"Department of Oral and Maxillofacial Surgery, Kagawa University School of Medicine, 1750-1 Ikenobe, Miki, Kagawa 761-0793, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Natsuo","family":"Ueda","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, Kagawa University School of Medicine, 1750-1 Ikenobe, Miki, Kagawa 761-0793, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,8,27]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/0163-7827(90)90004-5","article-title":"N-acylated glycerophospholipids and their derivatives","volume":"29","author":"Schmid","year":"1990","journal-title":"Prog. 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