Cellular arachidonate-releasing function of novel classes of secretory phospholipase A2s (groups III and XII).
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.
Murakami
Makoto
M
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
Masuda
Seiko
S
Shimbara
Satoko
S
Bezzine
Sofiane
S
Lazdunski
Michael
M
Lambeau
Gérald
G
Gelb
Michael H
MH
Matsukura
Satoshi
S
Kokubu
Fumio
F
Adachi
Mitsuru
M
Kudo
Ichiro
I
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
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