title: Calcium-independent phospholipase A2 mediates proliferation of human promonocytic U937 cells.
abstract: We have investigated the possible involvement of two intracellular phospholipases A(2), namely group VIA calcium-independent phospholipase A(2) (iPLA(2)-VIA) and group IVA cytosolic phospholipase A(2) (cPLA(2)alpha), in the regulation of human promonocytic U937 cell proliferation. Inhibition of iPLA(2)-VIA activity by either pharmacological inhibitors such as bromoenol lactone or methyl arachidonyl fluorophosphonate or using specific antisense technology strongly blunted U937 cell proliferation. In contrast, inhibition of cPLA(2)alpha had no significant effect on U937 proliferation. Evaluation of iPLA(2)-VIA activity in cell cycle-synchronized cells revealed highest activity at G(2)/M and late S phases, and lowest at G(1). Phosphatidylcholine levels showed the opposite trend, peaking at G(1) and lowest at G(2)/M and late S phase. Reduction of U937 cell proliferation by inhibition of iPLA(2)-VIA activity was associated with arrest in G(2)/M and S phases. The iPLA(2)-VIA effects were found to be independent of the generation of free arachidonic acid or one of its oxygenated metabolites, and may work through regulation of the cellular level of phosphatidylcholine, a structural lipid that is required for cell growth/membrane expansion.
authors.affiliation: Institute of Molecular Biology and Genetics, Spanish National Research Council (CSIC) and University of Valladolid School of Medicine, Spain.
authors.forename: María A
authors.initials: MA
authors.lastname: Balboa
authors.forename: Rebeca
authors.initials: R
authors.lastname: Pérez
authors.forename: Jesús
authors.initials: J
authors.lastname: Balsinde
mesh_terms: D016718:Arachidonic Acid / Q000378:metabolism; D002118:Calcium; D049109:Cell Proliferation / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000494:pharmacology; D054522:Group VI Phospholipases A2 / Q000037:antagonists & inhibitors / Q000378:metabolism*; D006801:Humans; D020298:U937 Cells
chemical_list: D004791:Enzyme Inhibitors; D016718:Arachidonic Acid; D054522:Group VI Phospholipases A2; D002118:Calcium