Sphingosine 1-phosphate induces arachidonic acid mobilization in A549 human lung adenocarcinoma cells.
In the present paper, the effect of sphingosine 1-phosphate (Sph-1-P) on arachidonic acid mobilization in A549 human lung adenocarcinoma cells was investigated. Sph-1-P provoked a rapid and relevant release of arachidonic acid which was similar to that elicited by bradykinin, well-known pro-inflammatory agonist. The Sph-1-P-induced release of arachidonic acid involved Ca(2+)-independent phospholipase A(2) (iPLA2) activity, as suggested by the dose-dependent inhibition exerted by the rather specific inhibitor bromoenol lactone. The Sph-1-P-induced release of arachidonic acid was pertussis toxin-sensitive, pointing at a receptor-mediated mechanism, which involves heterotrimeric Gi proteins. The action of Sph-1-P was totally dependent on protein kinase C (PKC) catalytic activity and seemed to involve agonist-stimulated phospholipase D (PLD) activity. This study represents the first evidence for Sph-1-P-induced release of arachidonic acid which occurs through a specific signaling pathway involving Gi protein-coupled receptor(s), PKC, PLD and iPLA2 activities.
Vasta
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V
Dipartimento di Scienze Biochimiche, Università degli Studi di Firenze, Viale Morgagni 50, 50134, Firenze, Italy.
Meacci
E
E
Catarzi
S
S
Donati
C
C
Farnararo
M
M
Bruni
P
P
D000230:Adenocarcinoma; D016718:Arachidonic Acid / Q000378:metabolism*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006801:Humans; D008053:Lipid Mobilization / Q000187:drug effects; D008175:Lung Neoplasms; D008246:Lysophospholipids; D010712:Phosphatidic Acids / Q000032:analysis; D010739:Phospholipase D / Q000378:metabolism; D010741:Phospholipases A / Q000378:metabolism; D011493:Protein Kinase C / Q000378:metabolism; D013110:Sphingosine / Q000031:analogs & derivatives* / Q000494:pharmacology; D014316:Tritium; D014407:Tumor Cells, Cultured
D004791:Enzyme Inhibitors; D008246:Lysophospholipids; D010712:Phosphatidic Acids; D014316:Tritium; C060506:sphingosine 1-phosphate; D016718:Arachidonic Acid; D011493:Protein Kinase C; D010741:Phospholipases A; D010739:Phospholipase D; D013110:Sphingosine