Group X secretory phospholipase A2 can induce arachidonic acid release and eicosanoid production without activation of cytosolic phospholipase A2 alpha.
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.
Saiga
Akihiko
A
Shionogi Research Laboratories, Shionogi and Co. Ltd., 3-1-1, Futaba-cho, Toyonaka, Osaka 561-0825, Japan.
Uozumi
Naonori
N
Ono
Takashi
T
Seno
Kaoru
K
Ishimoto
Yoshikazu
Y
Arita
Hitoshi
H
Shimizu
Takao
T
Hanasaki
Kohji
K
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
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