title: Cellular arachidonate-releasing function of novel classes of secretory phospholipase A2s (groups III and XII).
abstract: Here we report cellular arachidonate (AA) release and prostaglandin (PG) production by novel classes of secretory phospholipase A(2)s (sPLA(2)s), groups III and XII. Human group III sPLA(2) promoted spontaneous AA release, which was augmented by interleukin-1, in HEK293 transfectants. The central sPLA(2) domain alone was sufficient for its in vitro enzymatic activity and for cellular AA release at the plasma membrane, whereas either the unique N- or C-terminal domain was required for heparanoid-dependent action on cells to augment AA release, cyclooxygenase-2 induction, and PG production. Group III sPLA(2) was constitutively expressed in two human cell lines, in which other sPLA(2)s exhibited different stimulus inducibility. Human group XII sPLA(2) had a weak enzymatic activity in vitro and minimally affects cellular AA release and PG production. Cells transfected with group XII sPLA(2) exhibited abnormal morphology, suggesting a unique functional aspect of this enzyme. Based on the present results as well as our current analyses on the group I/II/V/X sPLA(2)s, general properties of cellular actions of a full set of mammalian sPLA(2)s in regulating AA metabolism are discussed.
authors.affiliation: Department of Health Chemistry, School of Pharmaceutical Sciences, Showa University, 1-5-8 Hatanodai, Shinagawa-ku, Tokyo 142-8555, Japan. mako@pharm.showa-u.ac.jp
authors.forename: Makoto
authors.initials: M
authors.lastname: Murakami
authors.forename: Seiko
authors.initials: S
authors.lastname: Masuda
authors.forename: Satoko
authors.initials: S
authors.lastname: Shimbara
authors.forename: Sofiane
authors.initials: S
authors.lastname: Bezzine
authors.forename: Michael
authors.initials: M
authors.lastname: Lazdunski
authors.forename: Gérald
authors.initials: G
authors.lastname: Lambeau
authors.forename: Michael H
authors.initials: MH
authors.lastname: Gelb
authors.forename: Satoshi
authors.initials: S
authors.lastname: Matsukura
authors.forename: Fumio
authors.initials: F
authors.lastname: Kokubu
authors.forename: Mitsuru
authors.initials: M
authors.lastname: Adachi
authors.forename: Ichiro
authors.initials: I
authors.lastname: Kudo
mesh_terms: D016718:Arachidonic Acid / Q000378:metabolism*; D002460:Cell Line; D051546:Cyclooxygenase 2; D015232:Dinoprostone / Q000096:biosynthesis; D054520:Group III Phospholipases A2; D006493:Heparin / Q000031:analogs & derivatives* / Q000494:pharmacology; D006801:Humans; D007527:Isoenzymes / Q000096:biosynthesis; D008565:Membrane Proteins; D010741:Phospholipases A / Q000032:analysis / Q000502:physiology*; D011451:Prostaglandin-Endoperoxide Synthases / Q000096:biosynthesis; D011509:Proteoglycans / Q000494:pharmacology
chemical_list: D007527:Isoenzymes; D008565:Membrane Proteins; D011509:Proteoglycans; C036090:heparin proteoglycan; D016718:Arachidonic Acid; D006493:Heparin; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human; D011451:Prostaglandin-Endoperoxide Synthases; D010741:Phospholipases A; D054520:Group III Phospholipases A2; C484163:PLA2G3 protein, human; D015232:Dinoprostone