STRUCTURE AND REGULATION OF ETHANOL-INDUCIBLE CYTOCHROME P450 GENE

摄食酒精诱导的微粒体酶也是 导致血清1，2-丙二醇升高的同一种酶 在酗酒者的血清中发现(Koop DR，Casazza JP，J Biol Chem 1985年；第260：13607-13612)。我们已经克隆了大鼠和人的编码基因 乙醇诱导的细胞色素P450(P450 IIE1)及其活性的测定 核苷酸，从而蛋白质序列。利用克隆的P450 IIE1基因 抗体对P450 IIE1基因表达的调节作用 检查过了。我们提出了三种不同类型的监管 P450 IIE1基因的表达：转录激活 发育；转录后激活(可能通过蛋白质 稳定性)通过各种诱导剂，例如乙醇、丙酮和 吡唑类化合物；糖尿病和糖尿病患者的mRNA稳定性 饥饿的动物。通过对大鼠基因组DNA的克隆和测序 P450 IIE1，我们已经证明了转录 P450 IIE1的激活仅是由于特定的去甲基化 P450 IIE1基因5‘端。通过测量以下人员的流动率 来自未经处理的对照组大鼠和丙酮处理的大鼠的P450 IIE1，我们 进一步表明，转录后激活通过不同的 外源诱导物是由特定的P450 IIE1蛋白引起的 稳定状态。

The microsomal enzyme induced by feeding of alcohol is also the same enzyme responsible for the elevation of serum 1,2-propanediol found in the serum of alcoholics (Koop DR, Casazza JP, J Biol Chem 1985;260:13607-13612). We have cloned rat and human cDNA encoding ethanol-inducible cytochrome P450 (P450 IIE1) and determined their nucleotide and thus protein sequences. Using cloned P450 IIE1 cDNA and antibodies, the regulation of P450 IIE1 gene expression was examined. We have proposed three distinct types of regulation of P450 IIE1 gene expression: transcriptional activation during development; post-transcriptional activation (probably via protein stabilization) by various inducers such as ethanol, acetone, and pyrazole derivatives; and mRNA stabilization in diabetes and starved animals. By cloning and sequencing of rat genomic DNA for P450 IIE1, we have demonstrated evidences that the transcriptional activation of P450 IIE1 is due to specific demethylation only at 5' end of the P450 IIE1 gene. By measuring the turnover rates of P450 IIE1 from untreated control rats and acetone-treated rats, we further suggest that post-transcriptional activation by various exogeneous inducers are due to specific P450 IIE1 protein stabilization.