Specific changes in the protein composition of rat liver in response to the peroxisome proliferators ciprofibrate, Wy-14,643 and di-(2-ethylhexyl)phthalate.
Specific changes in the protein composition of rat liver in response to the peroxisome proliferators ciprofibrate, Wy-14,643 and di-(2-ethylhexyl)phthalate.
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大鼠肝脏蛋白质组成对过氧化物酶体增殖剂环丙贝特、Wy-14,643 和邻苯二甲酸二(2-乙基己基)酯的特异性变化。
DOI：
10.1042/bj2270767
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发表时间：
1985
期刊：
影响因子：
--
通讯作者：
Reddy,JK
中科院分区：
文献类型：
--
作者：
Watanabe,T;Lalwani,ND;Reddy,JK
降血脂药物环丙贝特和Wy-14,643([4-chloro-6-(2，3-xylidino)-2-pyrimidinylthio]acetic酸)和邻苯二甲酸酯增塑剂邻苯二甲酸二(2-乙基己基)-邻苯二甲酸二(2-乙基己基)-邻苯二甲酸二乙酯和其他过氧化物酶体增殖剂一样，产生显著的肝肿大，诱导过氧化物体脂肪酸β-氧化酶系统，并在肝实质细胞中大量增殖。用高分辨双向凝胶电泳法分析了环丙贝特、Wy-14、643和DEHP诱导的大鼠肝组织过氧化物酶增殖后蛋白质组分的变化。用等电聚焦双向凝胶电泳法和非平衡pH梯度凝胶电泳法分别对正常大鼠和过氧化物体增殖剂处理大鼠全肝匀浆进行蛋白质分离。在全肝匀浆中，随着过氧化物酶体增殖的诱导，酸性凝胶中的6种蛋白质和碱性凝胶中的6种蛋白质的含量增加。使用过氧化物酶体增殖剂可抑制肝脏匀浆中的三种酸性蛋白。用多抗可溶性过氧化物酶体蛋白的多特异性抗血清和抗过氧化物酶体增殖相关的MR-80000多肽的单特异性抗血清免疫印迹的方法表明，这些过氧化物酶体增殖物诱导的碱性蛋白主要是过氧化物体蛋白。多肽PPA-80成为过氧化物酶体增殖物处理大鼠肝脏总匀浆中含量最丰富的蛋白质。这些结果表明，环丙贝特、DEHP和Wy-14,643诱导了特定肝脏蛋白的显著变化，其中一些变化可以作为识别一组基因产物的基线，这些基因产物可能有助于定义特定的“过氧化物酶增殖体结构域”。
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’.