STRUCTURE AND REGULATION OF ETHANOL-INDUCIBLE CYTOCHROME P450 GENE

摄食酒精诱导的微粒体酶也是 同样的酶负责升高血清1，2- 在酗酒者的血清中发现丙二醇(Koop，D.R.， 《生物化学杂志》260：13607-13612,1985年)。特定的 抗乙醇诱导的细胞色素P450多克隆抗体 (P450j，P450 IIE)在兔体内制备并用于分离 P450j的cDNA.编码大鼠和大鼠P450j的cDNA 对人进行了分离和鉴定。主要氨基酸 用核苷酸测定大鼠和人P450j的序列 大鼠P450j基因最长cDNA序列的测定 将序列与其他细胞色素P450的序列进行比较 确定结构相似性。 用克隆的P450j基因和抗体研究P450j的表达。 P450j基因在发育过程中的表达 诱导剂以及病理生理条件。通过组合 在cDNA杂交和免疫印迹分析中，有三种类型的 观察到P450j基因的表达：转录激活 在发育过程中；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、 和吡唑衍生物；糖尿病和糖尿病患者的mRNA稳定性 饥饿的动物。P450j在不同组织中的分布及调控 用克隆的P450j基因对组织进行了研究。

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, D.R., Casazza, J.P.: J Biol Chem 260: 13607-13612, 1985). Specific polyclonal antibody against ethanol-inducible cytochrome P450 (P450j, P450 IIE) was prepared in rabbit and utilized to isolate cDNA for P450j. The cDNAs encoding P450j of both rat and human were isolated and characterized. The primary amino acid sequences of rat and human P450j were determined by nucleotide sequencing of the longest cDNAs for P450j; The rat P450j sequence was compared to those of other cytochrome P450s to determine the structural similarity. Cloned P450j cDNA and antibodies were used to study the expression of P450j gene during development and by various inducers as well as pathophysiological conditions. By combination of cDNA hybridization and immunoblot analyses, three types of P450j gene expression were observed: 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. Distribution and regulation of P450j in different tissues were also studied by using cloned P450j cDNA.