LOCALIZATION OF PEROXISOME PROLIFERATOR-ACTIVATED RECEPTOR IN MOUSE AND RAT-TISSUES AND DEMONSTRATION OF ITS NUCLEAR TRANSLOCATION IN TRANSFECTED CV-1 CELLS

Hepatocarcinogenesis in rodents induced by nongenotoxic peroxisome pro liferators is postulated to be a receptor-mediated process. The peroxi some proliferator-activated receptors (PPAR) are members of the steroi d hormone receptor superfamily, which participate in ligand-dependent transcriptional activation of peroxisomal fatty acid beta oxidation en zyme system genes in liver parenchymal cells of rats and mice. In orde r to study the tissue distribution and cellular localization of PPAR, we raised polyclonal antibodies against PPAR using a recombinant rat P PAR (rPPAR) expressed as a glutathione-S-transferase-rPPAR fusion prot ein. On immunoblot analysis the antibodies specifically recognized a 5 5 kDa PPAR protein in rat, mouse and human liver homogenates. Immunobl otting also showed that in the mouse and rat, PPAR is expressed in liv er, kidney and heart, and only weakly in brain and testis. Immunohisto chemical localization in the rat and mouse revealed that PPAR is highl y expressed in perivenular (i.e., those surrounding hepatic vein) hepa tocytes and very weakly in the cytoplasm of remaining hepatocytes. In the kidney, PPAR was visualized predominantly in the p(3) segments of proximal convoluted tubular epithelium. CV-1 cells transiently transfe cted with rPPAR cDNA construct showed predominant cytoplasmic fluoresc ence; treatment of these cells with ciprofibrate, a peroxisome prolife rator, resulted in the nuclear translocation of PPAR signal.