PLA2 is important in phosphatidic acid-induced Bcl-2 expression through ERK1/2 MAPK activation

초록

Phosphatidic acid (PA), the product of PLD-mediated reaction, is lipid second messenger that participates in various intracellular signaling events and regulates a growing list of signaling protein. In this study, we tried to find out the mechanism of Bcl-2 up-regulation by diC8PA treatment in HeLa cell. Treatment with diC8PA resulted in significantly increased expression of Bcl-2 in HeLa cell. Moreover diC8PA-induced Bcl-2 expression was blocked by mepacrine, an inhibitor of phospholipase A2 (PLA2), whereas enhanced rather by propranolol, an inhibitor of diC8PA phospholydrolase (PAP). Treatment of 1,2-Dipalmitoryl-sn-Glycero-3-phosphate (DPPA) instead of diC8PA also increased Bcl-2 expression indicating that Bcl-2 expression is mediated through lysophosphatidic acid (LPA), not through arachidonic acid. To investigate the relation between ERK1/2 MAPK pathway and Bcl-2 expression, we used MEK1/2 inhibitor, PD98059. Pretreatment with PD98059 decreased diC8PA-induced Bcl-2 expression in HeLa cell, indicating that ERK1/2 MAPK was closely related with Bcl-2 expression. In addition, the ERK1/2 MAPK is also associated with LPA-induced Bcl-2 expression. When treated with PD98059, ERK1/2 MAPK activation and LPA-induced Bcl-2 expression were inhibited. Taken together, PLA2 is important in diC8PA-induced Bcl-2 expression by producing LPA which is involved in ERK1/2 MAPK activation.