title: Different functional aspects of the group II subfamily (Types IIA and V) and type X secretory phospholipase A(2)s in regulating arachidonic acid release and prostaglandin generation. Implications of cyclooxygenase-2 induction and phospholipid scramblase-mediated cellular membrane perturbation.
abstract: We have recently reported that members of the heparin-binding group II subfamily of secretory PLA(2)s (sPLA(2)s) (types IIA and V), when transfected into 293 cells, released [(3)H]arachidonic acid (AA) preferentially in response to interleukin-1 (IL-1) and acted as "signaling" PLA(2)s that were functionally coupled with prostaglandin biosynthesis. Here we show that these group II subfamily sPLA(2)s and the type X sPLA(2) behave in a different manner, the former being more efficiently coupled with the prostaglandin-biosynthetic pathway than the latter, in 293 transfectants. Type X sPLA(2), which bound only minimally to cell surface proteoglycans, augmented the release of both [(3)H]AA and [(3)H]oleic acid in the presence of serum but not IL-1. Both types IIA and V sPLA(2), the AA released by which was efficiently converted to prostaglandin E(2), markedly augmented IL-1-induced expression of cyclooxygenase (COX)-2 in a heparin-sensitive fashion, whereas type X sPLA(2) lacked the ability to augment COX-2 expression, thereby exhibiting the poor prostaglandin E(2)-biosynthetic response unless either of the COX isozymes was forcibly introduced into type X sPLA(2)-expressing cells. Implication of phospholipid scramblase, an enzyme responsible for the perturbation of plasma membrane asymmetry, revealed that the scramblase-transfected cells became more sensitive to types IIA and V, but not X, sPLA(2), releasing both [(3)H]AA and [(3)H]oleic acid in an IL-1-independent manner. Thus, although phospholipid scramblase-mediated alteration in plasma membrane asymmetry actually led to the increased cellular susceptibility to the group II subfamily of sPLA(2)s, several lines of evidence suggest that it does not entirely mimic their actions on cells after IL-1 signaling. Interestingly, coexpression of type IIA or V, but not X, sPLA(2) and phospholipid scramblase resulted in a marked reduction in cell growth, revealing an unexplored antiproliferative aspect of particular classes of sPLA(2).
authors.affiliation: Department of Health Chemistry, School of Pharmaceutical Sciences, Showa University, 1-5-8 Hatanodai, Shinagawa-ku, Tokyo 142, Japan.
authors.forename: M
authors.initials: M
authors.lastname: Murakami
authors.forename: T
authors.initials: T
authors.lastname: Kambe
authors.forename: S
authors.initials: S
authors.lastname: Shimbara
authors.forename: K
authors.initials: K
authors.lastname: Higashino
authors.forename: K
authors.initials: K
authors.lastname: Hanasaki
authors.forename: H
authors.initials: H
authors.lastname: Arita
authors.forename: M
authors.initials: M
authors.lastname: Horiguchi
authors.forename: M
authors.initials: M
authors.lastname: Arita
authors.forename: H
authors.initials: H
authors.lastname: Arai
authors.forename: K
authors.initials: K
authors.lastname: Inoue
authors.forename: I
authors.initials: I
authors.lastname: Kudo
mesh_terms: D017304:Annexin A5 / Q000378:metabolism; D016718:Arachidonic Acid / Q000378:metabolism*; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism*; D002462:Cell Membrane / Q000378:metabolism*; D051546:Cyclooxygenase 2; D015232:Dinoprostone / Q000096:biosynthesis; D005227:Fatty Acids / Q000378:metabolism; D054501:Group II Phospholipases A2; D006493:Heparin / Q000378:metabolism; D007375:Interleukin-1 / Q000494:pharmacology; D007527:Isoenzymes / Q000378:metabolism*; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D019301:Oleic Acid / Q000378:metabolism; D010741:Phospholipases A / Q000145:classification / Q000235:genetics / Q000378:metabolism*; D049294:Phospholipid Transfer Proteins; D011451:Prostaglandin-Endoperoxide Synthases / Q000378:metabolism*; D011453:Prostaglandins / Q000096:biosynthesis*; D011485:Protein Binding; D011994:Recombinant Proteins / Q000378:metabolism; D014162:Transfection
chemical_list: D017304:Annexin A5; D002352:Carrier Proteins; D005227:Fatty Acids; D007375:Interleukin-1; D007527:Isoenzymes; D008565:Membrane Proteins; D049294:Phospholipid Transfer Proteins; D011453:Prostaglandins; D011994:Recombinant Proteins; D016718:Arachidonic Acid; D019301:Oleic Acid; D006493:Heparin; D051546:Cyclooxygenase 2; D011451:Prostaglandin-Endoperoxide Synthases; D010741:Phospholipases A; D054501:Group II Phospholipases A2; D015232:Dinoprostone