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Calcium‐independent phospholipase A 2 mediates proliferation of human promonocytic U937 cells
Author(s) -
Balboa María A.,
Pérez Rebeca,
Balsinde Jesús
Publication year - 2008
Publication title -
the febs journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.981
H-Index - 204
eISSN - 1742-4658
pISSN - 1742-464X
DOI - 10.1111/j.1742-4658.2008.06350.x
Subject(s) - phospholipase a2 , u937 cell , arachidonic acid , phospholipase a , cell growth , biology , phospholipase , microbiology and biotechnology , cytosol , intracellular , phosphatidylcholine , calcium , calcium in biology , cell cycle , cell , biochemistry , phospholipid , medicine , apoptosis , enzyme , membrane
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 α), 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 α 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.