Modulation of cytosolic phospholipase A(2) by PPAR activators in human preadipocytes

Cytosolic phospholipase A(2) (cPLA(2)) is responsible for the release of ar achidonic acid, a precursor for eicosanoid biosynthesis, from cellular phos pholipids. The objective of this study is to examine the regulation of cPLA (2) by peroxisome proliferator-activated receptor (PPAR) activators in prea dipocyte SW872 (SW) cells. PPAR belong to the superfamily of nuclear hormon e 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, Clofib rate, a PPAR alpha activator, caused an enhancement of ionophore A-23187-in duced arachidonate release in SW cells. This increase resulted from an enha ncement of cPLA(2) activity, tvhich was caused by an increase in enzyme pro tein. Clofibrate at lower concentrations (10-200 muM) produced increases in the mRNA levels of cPLA(2) in a dose-response manner. At higher concentrat ions (>400 muM), clofibrate treatment resulted in the attenuation of the cP LA(2) mRNA level and protein expression.jlr We postulate that clofibrate, a cting through the PPAR alpha, caused an induction in the transcription of c PLA(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.