Modulation of cytosolic phospholipase A2 by PPAR activators in human preadipocytes

Cytosolic phospholipase A(2) (cPLA(2)) is responsible for the release of arachidonic acid, a precursor for eicosanoid biosynthesis, from cellular phospholipids. The objective of this study is to examine the regulation of cPLA(2) by peroxisome proliferator-activated receptor (PPAR) activators in preadipocyte SW872 (SW) cells. PPAR belong to the superfamily of nuclear hormone receptors that heterodimerize with the retinoid X receptor, In this study, the presence of both PPAR alpha and PPAR gamma was confirmed in SW cells by positive identification of their mRNA in the cellular homogenate, Clofibrate, a PPAR alpha activator, caused an enhancement of ionophore A-23187-induced arachidonate release in SW cells. This increase resulted from an enhancement of cPLA(2) activity, tvhich was caused by an increase in enzyme protein. Clofibrate at lower concentrations (10-200 muM) produced increases in the mRNA levels of cPLA(2) in a dose-response manner. At higher concentrations (>400 muM), clofibrate treatment resulted in the attenuation of the cPLA(2) mRNA level and protein expression.jlr We postulate that clofibrate, acting through the PPAR alpha, caused an induction in the transcription of cPLA(2) gene, which led to an increase in the cPLA(2) protein. The observed increase in arachidonate release in SW cells appeared to be a direct result of the enhanced cPLA(2) activity.