title: Group X secretory phospholipase A2 can induce arachidonic acid release and eicosanoid production without activation of cytosolic phospholipase A2 alpha.
abstract: Group X secretory phospholipase A2 (sPLA2-X) and cytosolic phospholipase A2 alpha (cPLA2alpha) are involved in the release of arachidonic acid (AA) from membrane phospholipids linked to the eicosanoid production in various pathological states. Recent studies have indicated the presence of various types of cross-talk between sPLA2s and cPLA2alpha resulting in effective AA release. Here we examined the dependence of sPLA2-X-induced potent AA release on the cPLA2alpha activation by using specific cPLA2alpha or sPLA2 inhibitors as well as cPLA2alpha-deficient mice. We found that Pyrrophenone, a cPLA2alpha-specific inhibitor, did not suppress the sPLA2-X-induced potent AA release and prostaglandin E2 formation in mouse spleen cells. Furthermore, the amount of AA released by sPLA2-X from spleen cells was not significantly altered by cPLA2alpha deficiency. These results suggest that sPLA2-X induces potent AA release without activation of cPLA2a, which might be relevant to eicosanoid production in some pathological states where cPLA2a is not activated.
authors.affiliation: Shionogi Research Laboratories, Shionogi and Co. Ltd., 3-1-1, Futaba-cho, Toyonaka, Osaka 561-0825, Japan.
authors.forename: Akihiko
authors.initials: A
authors.lastname: Saiga
authors.forename: Naonori
authors.initials: N
authors.lastname: Uozumi
authors.forename: Takashi
authors.initials: T
authors.lastname: Ono
authors.forename: Kaoru
authors.initials: K
authors.lastname: Seno
authors.forename: Yoshikazu
authors.initials: Y
authors.lastname: Ishimoto
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Arita
authors.forename: Takao
authors.initials: T
authors.lastname: Shimizu
authors.forename: Kohji
authors.initials: K
authors.lastname: Hanasaki
mesh_terms: D000818:Animals; D016718:Arachidonic Acid / Q000378:metabolism*; D000001:Calcimycin / Q000494:pharmacology; D002219:Carbamates / Q000494:pharmacology; D003600:Cytosol / Q000201:enzymology; D015777:Eicosanoids / Q000378:metabolism*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D054513:Group IV Phospholipases A2; D054509:Group X Phospholipases A2; D006801:Humans; D007212:Indolizines / Q000494:pharmacology; D007700:Kinetics; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D010740:Phospholipases / Q000037:antagonists & inhibitors; D010741:Phospholipases A / Q000378:metabolism*; D054467:Phospholipases A2; D011759:Pyrrolidines / Q000494:pharmacology; D011994:Recombinant Proteins / Q000378:metabolism; D013154:Spleen / Q000201:enzymology
chemical_list: D002219:Carbamates; D015777:Eicosanoids; D004791:Enzyme Inhibitors; D007212:Indolizines; D011759:Pyrrolidines; D011994:Recombinant Proteins; C119389:indoxam; C455981:pyrrophenone; D016718:Arachidonic Acid; D000001:Calcimycin; D010740:Phospholipases; D010741:Phospholipases A; D054513:Group IV Phospholipases A2; D054509:Group X Phospholipases A2; C516365:PLA2G10 protein, human; D054467:Phospholipases A2; C516366:Pla2g10 protein, mouse