Regulation of rat kidney mesangial cell phospholipase A₂

1. The precursor of eicosanoids is arachidonic acid, which emanates from the cleavage of the sn-2 position of phospholipids by phospholipase A₂ (PLA₂). Eicosanoids have diverse physiological and pathophysiological effects in the kidney. The regulation of phospholipase A₂ has important implications for kidney function. 2. In the current communication we focus our attention on mesangial cell cytosolic PLA₂ (cPLA₂) and its regulation at the post-translational and post-transcriptional level. 3. At the post-translational level, using site directed mutagenesis of cPLA₂ and a dominant negative ras, we have demonstrated that cPLA₂ can be phosphorylated by mitogen activated protein (MAP-2) kinase leading to increased cPLA₂ enzymatic activity. 4. At the post-transcriptional level we show that the half-life of cPLA₂ mRNA in mesangial cells is significantly increased when mesangial cells are stimulated by mitogens. We further demonstrate the presence of three ATTTA motifs in the 3′ untranslated region (′ UTR) of the cPLA₂ cDNA. 5. Using chimeric constructs bearing the 3′ UTR from rat cPLA₂ fused downstream of the luciferase reporter, we demonstrate that this region exerts a destabilizing effect on cPLA₂. 6. We have isolated and mapped genomic DNA and polymorphic markers for cPLA₂ in the human and rat.