title: Clearance of group X secretory phospholipase A(2) via mouse phospholipase A(2) receptor.
abstract: Given the potent hydrolyzing activity toward phosphatidylcholine, group X secretory phospholipase A(2) (sPLA(2)-X) elicits a marked release of arachidonic acid linked to the potent production of lipid mediators in various cell types. We have recently shown that sPLA(2)-X can also act as a ligand for mouse phospholipase A(2) receptor (PLA(2)R). Here, we found that sPLA(2)-X was internalized and degraded via binding to PLA(2)R associated with the diminished prostaglandin E(2) (PGE(2)) formation in PLA(2)R-expressing Chinese hamster ovary (CHO) cells compared to CHO cells. Indirect immunocytochemical analysis revealed that internalized sPLA(2)-X was co-localized with PLA(2)R in the punctate structures in PLA(2)R-expressing CHO cells. Moreover, in mouse osteoblastic MC3T3-E(1) cells that endogenously express the PLA(2)R, the internalized sPLA(2)-X was localized in lysosomes. These findings demonstrate that PLA(2)R acts as a clearance receptor for sPLA(2)-X to suppress its strong enzymatic activity.
authors.affiliation: Shionogi Research Laboratories, Shionogi and Co., Ltd., Sagisu 5-12-4, Fukushima-ku, 553-0002, Osaka, Japan.
authors.forename: Y
authors.initials: Y
authors.lastname: Yokota
authors.forename: M
authors.initials: M
authors.lastname: Notoya
authors.forename: K
authors.initials: K
authors.lastname: Higashino
authors.forename: Y
authors.initials: Y
authors.lastname: Ishimoto
authors.forename: K
authors.initials: K
authors.lastname: Nakano
authors.forename: H
authors.initials: H
authors.lastname: Arita
authors.forename: K
authors.initials: K
authors.lastname: Hanasaki
mesh_terms: D016475:3T3 Cells; D000818:Animals; D001692:Biological Transport; D016466:CHO Cells; D006224:Cricetinae; D015232:Dinoprostone / Q000096:biosynthesis; D054509:Group X Phospholipases A2; D008247:Lysosomes / Q000378:metabolism; D008657:Metabolic Clearance Rate; D051379:Mice; D010741:Phospholipases A / Q000378:metabolism*; D011956:Receptors, Cell Surface / Q000378:metabolism*; D054507:Receptors, Phospholipase A2
chemical_list: C516357:Pla2r1 protein, mouse; D011956:Receptors, Cell Surface; D054507:Receptors, Phospholipase A2; D010741:Phospholipases A; D054509:Group X Phospholipases A2; C516366:Pla2g10 protein, mouse; D015232:Dinoprostone