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首页> 美国卫生研究院文献>Proceedings of the National Academy of Sciences of the United States of America >Transcription 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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Transcription regulation of peroxisomal fatty acyl-CoA oxidase and enoyl-CoA hydratase/3-hydroxyacyl-CoA dehydrogenase in rat liver by peroxisome proliferators.

机译：过氧化物酶体增殖物对大鼠肝脏中过氧化物酶体脂肪酰基辅酶A氧化酶和烯酰基辅酶A水合酶/ 3-羟酰基辅酶A脱氢酶的转录调控

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摘要

The structurally diverse peroxisome proliferators ciprofibrate, clofibrate, and bis(2-ethylhexyl) phthalate [(EtHx)2 greater than 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 greater than 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 least 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 proliferators clofibrate, ciprofibrate, and (EtHx)2 greater than 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.
机译：结构不同的过氧化物酶体增殖物环丙酸酯，氯贝特酸酯和邻苯二甲酸双（2-乙基己基）酯[（EtHx）2大于Pht]增加了肝脏过氧化氢酶和过氧化物酶体脂肪酸β-氧化酶的活性，同时使过氧化物酶体在肝细胞中大量增殖。为了描述这些酶在肝脏中的诱导水平，脂肪酰基辅酶A氧化酶（FAOxase）和烯酰基辅酶A水合酶/ 3-羟酰基辅酶A脱氢酶双功能酶（PBE）的特定基因的转录活性在胃内给予环丙贝特，氯贝特或（EtHx）2单次大于Pht后，从雄性大鼠获得的分离的肝细胞核中测量了过氧化物酶体β-氧化系统的前两种酶和过氧化氢酶。所有这三种过氧化物酶体增生剂均迅速增加了肝脏中FAOxase和PBE基因的转录速率，在接近1小时后达到了接近最大速率（控制的9-15倍），并持续至给药该化合物后至少16小时。单次过氧化物酶体增殖剂给药后，通过印迹杂交分析测量的FAOxase和PBE mRNA水平以及通过免疫印迹分析的FAOxase和PBE蛋白含量同时增加，至少持续16小时。过氧化氢酶的mRNA水平增加了约1.4倍，但过氧化氢酶基因的转录速率未受到明显影响。结果表明，过氧化物酶体增殖物clofibrate，ciprofibrate和（EtHx）2大于Pht选择性地增加了过氧化物酶体脂肪酸β-氧化酶基因的转录速率。转录作用是否由过氧化物酶体增殖物-受体复合物介导尚待阐明。

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