Balboa María A, Pérez Rebeca, Balsinde Jesús
Institute of Molecular Biology and Genetics, Spanish National Research Council (CSIC) and University of Valladolid School of Medicine, Spain.
FEBS J. 2008 Apr;275(8):1915-24. doi: 10.1111/j.1742-4658.2008.06350.x. Epub 2008 Mar 8.
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.
我们研究了两种细胞内磷脂酶A2，即ⅥA组钙非依赖性磷脂酶A2（iPLA2-VIA）和ⅣA组胞质磷脂酶A2（cPLA2α），在人原单核细胞U937细胞增殖调控中的可能作用。使用诸如溴烯醇内酯或甲基花生四烯酰氟磷酸酯等药理学抑制剂，或采用特定的反义技术抑制iPLA2-VIA活性，均能显著抑制U937细胞增殖。相比之下，抑制cPLA2α对U937细胞增殖无显著影响。对细胞周期同步化细胞中的iPLA2-VIA活性进行评估发现，在G2/M期和S期后期活性最高，而在G1期最低。磷脂酰胆碱水平呈现相反趋势，在G1期达到峰值，在G2/M期和S期后期最低。通过抑制iPLA2-VIA活性来降低U937细胞增殖与细胞阻滞于G2/M期和S期有关。研究发现，iPLA2-VIA的作用与游离花生四烯酸或其氧化代谢产物之一的生成无关，可能是通过调节磷脂酰胆碱的细胞水平来发挥作用，磷脂酰胆碱是一种细胞生长/膜扩张所需的结构脂质。
