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SYMPOSIUM: Experimental Biology 1995 Role of Mesangial Cell Ion Transport in Glomerular Physiology and Disease: REGULATION OF RAT KIDNEY MESANGIAL CELL PHOSPHOLIPASE A 2
Author(s) -
Hack Nashrudeen,
Tay Agnes,
Schultz Aylit,
Muzin Nicholas,
Clayman Paula,
Egan Sean,
Skorecki Karl L
Publication year - 1996
Publication title -
clinical and experimental pharmacology and physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.752
H-Index - 103
eISSN - 1440-1681
pISSN - 0305-1870
DOI - 10.1111/j.1440-1681.1996.tb03065.x
Subject(s) - mesangial cell , phospholipase a2 , biology , post translational regulation , microbiology and biotechnology , untranslated region , transcriptional regulation , kinase , translational regulation , protein kinase a , messenger rna , transcription factor , kidney , endocrinology , phosphorylation , translation (biology) , biochemistry , enzyme , gene
SUMMARY1 The precursor of eicosanoids is arachidonic acid, which emanates from the cleavage of the sn‐2 position of phospholipids by phospholipase A 2 (PLA 2 ). Eicosanoids have diverse physiological and pathophysiological effects in the kidney. The regulation of phospholipase A 2 has important implications for kidney function. 2 In the current communication we focus our attention on mesangial cell cytosolic PLA 2 (cPLA 2 ) and its regulation at the post‐translational and post‐transcriptional level. 3 At the post‐translational level, using site directed mutagenesis of cPLA 2 and a dominant negative ras , we have demonstrated that cPLA 2 can be phosphorylated by mitogen activated protein (MAP‐2) kinase leading to increased cPLA 2 enzymatic activity. 4 At the post‐transcriptional level we show that the half‐life of cPLA 2 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 (3′ UTR) of the cPLA 2 cDNA. 5 Using chimeric constructs bearing the 3′ UTR from rat cPLA 2 fused downstream of the luciferase reporter, we demonstrate that this region exerts a destabilizing effect on cPLA 2 . 6 We have isolated and mapped genomic DNA and polymorphic markers for cPLA 2 in the human and rat.