Modulation of cytosolic phospholipase A2 by PPAR activators in human preadipocytes

Abstract

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 ␣ and PPAR ␥ was confirmed in SW cells by positive identification of their mRNA in the cellular homogenate. Clofibrate, a PPAR ␣ activator, caused an enhancement of ionophore A-23187-induced arachidonate release in SW cells. This increase resulted from an enhancement of cPLA 2 activity, which was caused by an increase in enzyme protein. Clofibrate at lower concentrations (10-200 M) produced increases in the mRNA levels of cPLA 2 in a dose-response manner. At higher concentrations ( Ͼ 400 M), clofibrate treatment resulted in the attenuation of the cPLA 2 mRNA level and protein expression. We postulate that clofibrate, acting through the PPAR ␣ , 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. -Jiang, Y.