Phospholipase A(2) activity in ox-LDL-stimulated mesangial cells and modulation by alpha-tocopherol

Background. Oxidized LDL increases the production of both prostaglandin E-2 (PGE(2)) and thromboxane B-2 (TXB2) in rat mesangial cells. These increase s were suppressed by antioxidants such as alpha-tocopherol (alpha-Toc) or p robucol. Methods. We investigated the mechanism by which oxidized LDL leads to an in crease in PGE(2) production using rat mesangial cells in culture. We also e xamined how alpha-Toc supresses this augmentation, by measuring intracellul ar Ca2+ and phospholipase A(2) (PLA(2)) activity. Results. In rat mesangial cells, oxidized LDL increased PLA(2) activity by increasing the intracellular calcium ion content, which resulted in the ind uction of PGE(2) production. On the other hand, pretreatment of cells with alpha-Toc, which resulted in a large uptake of alpha-Toc in cell membranes, markedly suppressed the augmentation of PGE(2) production and PLA(2) activ ity by oxidized LDL in a dose dependent manner. However, cytosolic PLA(2) p artially purified from mesangial cells was not inhibited by alpha-Toc despi te an increase of alpha-Toc. Conclusion. These results suggest that the augmentation of PLA(2) activity in mesangial cells by oxidized LDL is a result of oxidative stresses, and t hat the antioxidant action of alpha-Toc is responsible for the suppression of augmentation of PLA, activity observed in mesangial cells exposed to oxi dized LDL.