TAILIEUCHUNG - Báo cáo khoa học: Calcium-independent phospholipase A2 mediates proliferation of human promonocytic U937 cells

We have investigated the possible involvement of two intracellular phos-pholipases A2, namely group VIA calcium-independent phospholipase A2 (iPLA2-VIA) and group IVA cytosolic phospholipase A2 (cPLA2a), in the regulation of human promonocytic U937 cell proliferation. | ỊFEBS Journal Calcium-independent phospholipase A2 mediates proliferation of human promonocytic U937 cells Maria A. Balboa Rebeca Perez and Jesus Balsinde Institute of Molecular Biology and Genetics Spanish NationalResearch Council CSIC and University of Valladolid Schoolof Medicine Spain Keywords cell cycle human promonocytes membrane phospholipid phospholipase A2 proliferation Correspondence J. Balsinde Instituto de Biologia y Genetica Molecular Calle Sanz y Fores s n 47003 Valladolid Spain Fax 34 983 423 588 Tel 34 983 423 062 E-mail jbalsinde@ Received 26 December 2007 revised 15 February 2008 accepted 21 February 2008 doi 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 cPLA2a 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 cPLA2a 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. The phospholipase A2 PLA2 superfamily is a heterogeneous group of enzymes with distinct roles in cell function 1-5 .

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