Watanabe T, Lalwani N D, Reddy J K
Biochem J. 1985 May 1;227(3):767-75. doi: 10.1042/bj2270767.
The hypolipidaemic agents ciprofibrate and Wy-14,643 ([4-chloro-6-(2,3-xylidino)-2-pyrimidinylthio]acetic acid) and the phthalate-ester plasticizer di-(2-ethylhexyl)-phthalate (DEHP), like other peroxisome proliferators, produce a significant hepatomegaly and induce the peroxisomal fatty acid beta-oxidation enzyme system together with profound proliferation of peroxisomes in hepatic parenchymal cells. Changes in the profile of liver proteins in rats following induction of peroxisome proliferation by ciprofibrate, Wy-14,643 and DEHP have been analysed by high-resolution two-dimensional gel electrophoresis. The proteins of whole liver homogenates from normal and peroxisome-proliferator-treated rats were separated by two-dimensional gel electrophoresis using isoelectric focusing for acidic proteins and nonequilibrium pH gradient electrophoresis for basic proteins. In the whole liver homogenates, the quantities of six proteins in acidic gels and six proteins in the basic gels increased following induction of peroxisome proliferation. Peroxisome proliferator administration caused a repression of three acidic proteins in the liver homogenates. By the immunoblot method using polyspecific antiserum against soluble peroxisomal proteins and monospecific antiserum against peroxisome proliferation associated Mr 80000 polypeptide (polypeptide PPA-80), the majority of basic proteins induced by these peroxisome proliferators appeared to be peroxisomal proteins. Polypeptide PPA-80 becomes the most abundant protein in the total liver homogenates of peroxisome-proliferator-treated rats. These results indicate that ciprofibrate, DEHP and Wy-14,643 induce marked changes in the profile of specific hepatic proteins and that some of these changes should serve as a baseline to identify a set of gene products that may assist in defining the specific 'peroxisome proliferator domain'.
降血脂药物环丙贝特和Wy-14,643（[4-氯-6-(2,3-二甲苯胺基)-2-嘧啶基硫代]乙酸）以及邻苯二甲酸酯类增塑剂邻苯二甲酸二（2-乙基己基）酯（DEHP），与其他过氧化物酶体增殖剂一样，会导致明显的肝肿大，并诱导过氧化物酶体脂肪酸β-氧化酶系统以及肝实质细胞中过氧化物酶体的大量增殖。通过高分辨率二维凝胶电泳分析了环丙贝特、Wy-14,643和DEHP诱导大鼠过氧化物酶体增殖后肝脏蛋白质谱的变化。使用酸性蛋白质的等电聚焦和碱性蛋白质的非平衡pH梯度电泳，通过二维凝胶电泳分离正常大鼠和用过氧化物酶体增殖剂处理的大鼠的全肝匀浆蛋白。在全肝匀浆中，过氧化物酶体增殖诱导后，酸性凝胶中的六种蛋白质和碱性凝胶中的六种蛋白质的含量增加。给予过氧化物酶体增殖剂导致肝脏匀浆中三种酸性蛋白质受到抑制。通过使用针对可溶性过氧化物酶体蛋白的多特异性抗血清和针对与过氧化物酶体增殖相关的80000 Mr多肽（多肽PPA-80）的单特异性抗血清的免疫印迹法，这些过氧化物酶体增殖剂诱导的大多数碱性蛋白质似乎是过氧化物酶体蛋白。多肽PPA-80成为用过氧化物酶体增殖剂处理的大鼠全肝匀浆中最丰富的蛋白质。这些结果表明，环丙贝特、DEHP和Wy-14,643诱导了特定肝脏蛋白质谱的显著变化，其中一些变化应作为确定一组可能有助于定义特定“过氧化物酶体增殖剂结构域”的基因产物的基线。
