Segregated functions of two cytosolic phospholipase A2 isoforms (cPLA2α and cPLA2ε) in lipid mediator generation

• DOI: 10.1016/j.bcp.2022.115176
• Publication Date: 2022-07-14T01:30:43Z
• Authors: Makoto Murakami; Rina Takamiya; Yoshimi Miki; Nao Sugimoto; Yuki Nagasaki; Toshiko Suzuki-Ya...; Yoshitaka Taketomi
• Keywords: Mice; Phospholipases A2; 0303 health sciences; 03 medical and health sciences; Cytosol; Animals; Eicosanoids; Protein Isoforms; Lipid Metabolism

Among the phospholipase A2 (PLA2) superfamily, group IVA cytosolic PLA2 (cPLA2α) is currently attracting much attention as a central regulator of arachidonic acid (AA) metabolism linked to eicosanoid biosynthesis. Following cell activation, cPLA2α selectively releases AA, precursor variety eicosanoids, from phospholipids in perinuclear membrane compartments. cPLA2α-null mice display various phenotypes that could be largely explained by reduced signaling. In contrast, IVE cPLA2ε, another member cPLA2 family, acts Ca2+-dependent N-acyltransferase rather than PLA2, thereby regulating biosynthesis N-acylethanolamines (NAEs), unique class lipid mediators with an anti-inflammatory effect. response Ca2+ signaling, cPLA2ε translocates phosphatidylserine-rich organelle membranes endocytic/recycling pathway. vivo, induced keratinocytes psoriatic skin, and its genetic deletion exacerbates inflammation due marked reduction NAE-related lipids. also contributes NAE generation several if not all mouse tissues. Thus, two members catalyze distinct enzymatic reactions mobilize sets mediators, differently pathophysiological events health disease. Such segregation cPLA2α-eicosanoid cPLA2ε-NAE pathways represents new paradigm research on PLA2s mediators.