REGULATION OF ETHANOL-INDUCIBLE CYTOCHROME P450 GENE

作为一个持续进行的项目，分子调控机制 对P450IIE进行了进一步研究。我们之前已经确定和 乙醇诱导的细胞色素P450的结构测定 (P450IIE1)。我们还展示了三个 P450IIE1在大鼠体内的不同调节类型。三种类型的 P450IIE在肝、肺和肾中表达上调 纸巾。外源调控P450IIE1的分子机制 进一步调查了监管者和怀孕期间的情况。 脂肪诱导酮中毒过程中P450IIE1的翻译前激活 其信使核糖核酸水平的升高与血清中 乙酰乙酸酯和β-羟基丁酸酯，但不包括丙酮 激活P450IIE1，但不提高其mRNA水平。特定的 异烟肼和N-杂环对P450IIE1的翻译诱导作用 展示了诸如吡嗪之类的化合物。翻译前归约 孕期P450IIE和分娩时快速逆转 学习。妊娠晚期P450IIE1的降低提示 我们目前所处的负性荷尔蒙控制机制 正在调查。相比之下，戊氧基间苯二酚O-依赖戊基酶(相关 带有P450IIB1/B2)被相同的诱导剂翻译前激活， 吡啶。正在开发一种快速而灵敏的P450IIE1检测方法 人淋巴细胞表达P450IIE1的检测

As a continuous ongoing project, the molecular regulatory mechanism of P450IIE was further investigated. We have previously identified and determined the structures of the ethanol-inducible cytochrome P450 (P450IIE1) of both rat and human. We have also demonstrated three distinct types of regulation of P450IIE1 in rat. The three types of upregulation of P450IIE appeared to be present in liver, lung and kidney tissues. The molecular mechanism of P450IIE1 regulation by other exogenous regulators and during pregnancy were further investigated. Pretranlational activation of P450IIE1 during ketosis induced by a fat diet where the elevation of its mRNA level correlated with the levels of acetoacetate and beta-hydroxybutyrate but not with that of acetone which activates P450IIE1 without elevating its mRNA level. Specific translational induction of P450IIE1 by isoniazid and N-heterocyclic compounds such as pyrazine was demonstrated. Pretranslational reduction of P450IIE during pregnancy and rapid reversal upon parturition were studied. The reduction of P450IIE1 during late-term pregnancy indicates a negative hormonal control mechanism which we are currently investigating. In contrast, pentoxyresorufin O-depentylase (associated with P450IIB1/B2) was pretranslationally activated by the same inducer, pyridine. A rapid and sensitive assay for P450IIE1 is being developed for the detection of P450IIE1 expressed in human lymphocytes.