PEROXISOME PROLIFERATOR-BINDING PROTEIN - IDENTIFICATION AND PARTIAL CHARACTERIZATION OF NAFENOPIN-BINDING, CLOFIBRIC ACID-BINDING, AND CIPROFIBRATE-BINDING PROTEINS FROM RAT-LIVER
PEROXISOME PROLIFERATOR-BINDING PROTEIN - IDENTIFICATION AND PARTIAL CHARACTERIZATION OF NAFENOPIN-BINDING, CLOFIBRIC ACID-BINDING, AND CIPROFIBRATE-BINDING PROTEINS FROM RAT-LIVER
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DOI：
10.1073/pnas.84.15.5242
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发表时间：
1987-08-01
影响因子：
11.1
通讯作者：
REDDY, JK
中科院分区：
文献类型：
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作者：
LALWANI, ND;ALVARES, K;REDDY, JK
过氧化物酶体增殖（PP）在大鼠和小鼠肝脏中诱导高度可预测的多效性反应，其特征为肝肿大、肝细胞中过氧化物酶体数量增加和某些过氧化物酶体酶的诱导。采用亲和层析和离子交换层析两步法从大鼠肝胞液中纯化PP结合蛋白（PPbP）。三个PP，那非诺平及其结构类似物氯贝酸和环丙贝特，被用作亲和配体和洗脱剂。该方法产生的主要蛋白质在还原剂存在下在NaDodSO 4/PAGE上的表观Mr为70，000，在非变性条件下在凝胶过滤和聚丙烯酰胺梯度凝胶电泳上的Mr为140，000（Mr 140，000 - 160，000），表明活性蛋白质是二聚体。该蛋白质在非变性条件下具有4.2的酸性pI，在变性条件下上升至5.6。用三种不同但结构相关的试剂作为亲和配体分离相同的Mr 70，000蛋白质，以及分离的蛋白质的免疫学特性构成了强有力的证据，证明该蛋白质是能够识别与氯贝特结构相关的PP的PPbP。PPbP可能在PP诱导的多效性反应中起重要调节作用。
Peroxisome proliferative (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 at 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.