Calcium-independent phospholipase A2 mediates proliferation of human promonocytic U937 cells


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Abstract

We have investigated the possible involvement of two intracellular phospholipases A2, namely group VIA calcium-independent phospholipase A2 (iPLA2-VIA) and group IVA cytosolic phospholipase A2 (cPLA2α), in the regulation of human promonocytic U937 cell proliferation. Inhibition of iPLA2-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 cPLA2α had no significant effect on U937 proliferation. Evaluation of iPLA2-VIA activity in cell cycle-synchronized cells revealed highest activity at G2/M and late S phases, and lowest at G1. Phosphatidylcholine levels showed the opposite trend, peaking at G1 and lowest at G2/M and late S phase. Reduction of U937 cell proliferation by inhibition of iPLA2-VIA activity was associated with arrest in G2/M and S phases. The iPLA2-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.

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