TRANSCRIPTIONAL REGULATION OF PEROXISOMAL FATTY ACYL-COA OXIDASE AND ENOYL-COA HYDRATASE/3-HYDROXYACYL-COA DEHYDROGENASE IN RAT-LIVER BY PEROXISOME PROLIFERATORS
TRANSCRIPTIONAL REGULATION OF PEROXISOMAL FATTY ACYL-COA OXIDASE AND ENOYL-COA HYDRATASE/3-HYDROXYACYL-COA DEHYDROGENASE IN RAT-LIVER BY PEROXISOME PROLIFERATORS
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DOI：
10.1073/pnas.83.6.1747
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发表时间：
1986-03-01
影响因子：
11.1
通讯作者：
RAO, MS
中科院分区：
文献类型：
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作者：
REDDY, JK;GOEL, SK;RAO, MS
结构多样的过氧化物酶体增殖剂环丙贝特、氯贝特和邻苯二甲酸双（2-乙基己基）酯[(EtHx)2 > Pht]增加了肝脏过氧化氢酶和过氧化物酶体脂肪酸的活性。-氧化酶与肝细胞中过氧化物酶体的深度增殖有关。为了描述这些酶在肝脏中诱导的水平，研究了脂肪酰基辅酶a氧化酶（FAOxase）和烯酰辅酶a水合酶/3-羟基酰基辅酶a脱氢酶双功能酶（PBE）的特定基因的转录活性，这是过氧化物酶体的前两种酶。-氧化系统和过氧化氢酶在雄性大鼠分离的肝细胞核中进行了测量，这些大鼠在单次灌胃剂量的环丙贝特、氯贝特或（EtHx）2 > Pht后获得。所有三种过氧化物酶体增殖剂都能迅速增加肝脏中FAOxase和PBE基因的转录率，在给药后1小时达到接近最大速率（9-15倍于对照），并持续到给药后至少16小时。FAOxase和PBE mRNA水平，通过印迹杂交分析和FAOxase和PBE蛋白含量，通过免疫印迹分析，在单剂量过氧化物酶体增殖剂后至少16小时同时增加。过氧化氢酶mRNA水平升高约1.4倍，但对过氧化氢酶基因转录率无显著影响。结果表明，过氧化物酶体增殖性的氯贝特、环丙贝特和（EtHx） 2>pht选择性地增加了过氧化物酶体脂肪酸β的转录率。-氧化酶基因。转录效应是否由过氧化物酶体增殖体受体复合物介导仍有待阐明。
The structurally diverse peroxisome proliferators ciprofibrate, clofibrate, and bis(2-ethylhexyl) phthlate [(EtHx)2 > Pht] increase the activities of hepatic catalase and peroxisomal fatty acid .beta.-oxidation enzymes in conjunction with profound proliferation of peroxisomes in hepatocytes. In order to delineate the level at which these enzymes are induced in the liver, the transcriptional activity of specific genes for fatty acyl-CoA oxidase (FAOxase) and enoyl-CoA hydratase/3-hydroxyacyl-CoA dehydrogenase bifunctional enzyme (PBE), the first two enzymes of the peroxisomal .beta.-oxidation system, and for catalase were measured in isolated hepatocyte nuclei obtained from male rats following a single intragastric dose of ciprofibrate, clofibrate, or (EtHx)2 > Pht. All three peroxisome proliferators rapidly increased the rate of FAOxase and PBE gene transcription in liver, with near maximal rates (9-15 times control) reached by 1 hr and persisting until at leat 16 hr after administration of the compound. FAOxase and PBE mRNA levels, measured by blot-hybridization analysis and FAOxase and PBE protein content, analyzed by immunoblotting, increased concurrently up to at least 16 hr following a single dose of peroxisome proliferator. The catalase mRNA level increased about 1.4-fold, but the transcription rate of the catalase gene was not significantly affected. The results show that the peroxisome proliferative clofibrate, ciprofibrate, and (EtHx)2 > Pht selectively increase the rate of transcription of peroxisomal fatty acid .beta.-oxidation enzyme genes. Whether the transcriptional effects are mediated by peroxisome proliferator receptor complexes remains to be elucidated.