Involvement of the γ Isoform of cPLA2 in the Biosynthesis of Bioactive N-Acylethanolamines.
Molecules
; 26(17)2021 Aug 27.
Article
in En
| MEDLINE
| ID: mdl-34500646
ABSTRACT
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 É isoform of cytosolic phospholipase A2 (cPLA2) functions as an N-acyltransferase to form NAPE. Since the cPLA2 family consists of six isoforms (α, ß, γ, δ, É, and ζ), the present study investigated a possible involvement of isoforms other than É 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 É-expressing cells. Secondly, when the cells co-expressing É 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 É and γ isoforms. Furthermore, the purified cPLA2γ 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 cPLA2γ is involved in the biosynthesis of NAE by its phospholipase A1/A2 and lysophospholipase activities.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Protein Isoforms
/
Ethanolamines
/
Phospholipases A2
Limits:
Animals
/
Humans
/
Male
Language:
En
Journal:
Molecules
Journal subject:
BIOLOGIA
Year:
2021
Document type:
Article
Affiliation country:
Japón