Modulation of cytosolic phospholipase A2 by PPAR activators in human preadipocytes

Abstract

Cytosolic phospholipase A2 (cPLA2) 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 cPLA2 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 α and PPAR γ was confirmed in SW cells by positive identification of their mRNA in the cellular homogenate. Clofibrate, a PPAR α activator, caused an enhancement of ionophore A-23187-induced arachidonate release in SW cells. This increase resulted from an enhancement of cPLA2 activity, which was caused by an increase in enzyme protein. Clofibrate at lower concentrations (10–200 μM) produced increases in the mRNA levels of cPLA2 in a dose-response manner. At higher concentrations (>400 μM), clofibrate treatment resulted in the attenuation of the cPLA2 mRNA level and protein expression.We postulate that clofibrate, acting through the PPAR α, caused an induction in the transcription of cPLA2 gene, which led to an increase in the cPLA2 protein. The observed increase in arachidonate release in SW cells appeared to be a direct result of the enhanced cPLA2 activity.

Keywords

• cPLA2
• PPAR α
• clofibrate
• preadipocytes
• arachidonic acid
• SW cells