Peroxisome proliferator-binding protein: identification and partial characterization of nafenopin-, clofibric acid-, and ciprofibrate-binding proteins from rat liver.
Peroxisome proliferators (PP) induce a highly predictable pleiotropic response in rat and mouse liver that is characterized by hepatomegaly, increase in peroxisome number in hepatocytes, and induction of certain peroxisomal enzymes. The PP-binding protein (PPbP) was purified from rat liver cytosol by a two-step procedure involving affinity chromatography and ion-exchange chromatography. Three PP, nafenopin and its structural analogs clofibric acid and ciprofibrate, were used as affinity ligands and eluting agents. This procedure yields a major protein with an apparent Mr of 70,000 on NaDodSO4/PAGE in the presence of reducing agent and Mr 140,000 (Mr 140,000-160,000) on gel filtration and polyacrylamide gradient gel electrophoresis under nondenaturing conditions, indicating that the active protein is a dimer. This protein has an acidic pI of 4.2 under nondenaturing conditions, which rises to 5.6 under denaturing conditions. The isolation of the same Mr 70,000 protein with three different, but structurally related, agents as affinity ligands and the immunological identity of the isolated proteins constitute strong evidence that this protein is the PPbP capable of recognizing PP that are structurally related to clofibrate. The PPbP probably plays an important role in the regulation of PP-induced pleiotropic response.
D000818:Animals; D002352:Carrier Proteins / Q000302:isolation & purification* / Q000378:metabolism; D002994:Clofibrate / Q000031:analogs & derivatives*; D002995:Clofibric Acid / Q000031:analogs & derivatives* / Q000378:metabolism*; D058607:Fibric Acids; D047908:Intracellular Signaling Peptides and Proteins; D008099:Liver / Q000032:analysis*; D008297:Male; D008970:Molecular Weight; D009255:Nafenopin / Q000378:metabolism*; D011422:Propionates / Q000378:metabolism*; D051381:Rats; D011916:Rats, Inbred F344
D002352:Carrier Proteins; D058607:Fibric Acids; D047908:Intracellular Signaling Peptides and Proteins; D011422:Propionates; C052998:peroxisome proliferator-binding protein, rat; D009255:Nafenopin; D002995:Clofibric Acid; C019304:ciprofibrate; D002994:Clofibrate