RT info:eu-repo/semantics/article T1 Cellular plasmalogen content does not influence arachidonic acid levels or distribution in macrophages: A role for cytosolic phospholipase A2γ in phospholipid remodeling A1 Lebrero Fernández, Patricia A1 Astudillo, Alma M. A1 Astudillo del Valle, Alma María A1 Rubio, Julio M. A1 Fernández-Caballero Palomeque, Lidia A1 Kokotos, George A1 Balboa García, María Ángeles A1 Balsinde Rodríguez, Jesús K1 Arachidonic acid K1 Ácido araquidónico K1 Eicosanoids K1 Eicosanoides K1 Phospholipases K1 Fosfolipasas K1 Monocytes K1 Monocitos K1 Macrophages K1 Macrófagos AB Availability of free arachidonic acid (AA) constitutes a rate limiting factor for cellular eicosanoid synthesis. AA distributes differentially across membrane phospholipids, which is largely due to the action of coenzyme A-independent transacylase (CoA-IT), an enzyme that moves the fatty acid primarily from diacyl phospholipid species to ether-containing species, particularly the ethanolamine plasmalogens. In this work, we examined the dependence of AA remodeling on plasmalogen content using the murine macrophage cell line RAW264.7 and its plasmalogen-deficient variants RAW.12 and RAW.108. All three strains remodeled AA between phospholipids with similar magnitude and kinetics, thus demonstrating that cellular plasmalogen content does not influence the process. Cell stimulation with yeast-derived zymosan also had no effect on AA remodeling, but incubating the cells in AA-rich media markedly slowed down the process. Further, knockdown of cytosolic-group IVC phospholipase A2γ (cPLA2γ) by RNA silencing significantly reduced AA remodeling, while inhibition of other major phospholipase A2 forms such as cytosolic phospholipase A2α, calcium-independent phospholipase A2β, or secreted phospholipase A2 had no effect. These results uncover new regulatory features of CoA-IT-mediated transacylation reactions in cellular AA homeostasis and suggest a hitherto unrecognized role for cPLA2γ in maintaining membrane phospholipid composition via regulation of AA remodeling. PB MDPI SN 2073-4409 YR 2019 FD 2019 LK https://uvadoc.uva.es/handle/10324/55855 UL https://uvadoc.uva.es/handle/10324/55855 LA eng NO Cells, 2019, vol. 8, n. 8, 799 NO Producción Científica DS UVaDOC RD 01-may-2024