REGULATION OF ETHANOL-INDUCIBLE CYTOCHROME P450 GENE

我们以前克隆并证明了四种不同类型的调节， P45011E1。在过去的一年里，我们演示了两种额外的机制 异烟肼对P45011 E1的翻译激活作用 和吡嗪;和肝P45 OlIE 1的翻译前抑制， 怀孕异烟肼对P45 OlIE 1的特异性翻译诱导作用及 证明了吡嗪。然而，哒嗪和嘧啶，两个 吡嗪的立体异构体，不激活P45 OlIE 1，表明更多的 P450 11 E1 mRNA翻译成其 蛋白相比之下，具有五元环结构的吡咯 P45 OlIE 1活性由以下快速逆转（1天内）引起： 分娩也被证明。外源性类固醇 （孕酮、雌激素和甲状腺素）和肽类生长因子 （胎盘催乳素，催乳素和生长激素）没有引起 P45 OlIE 1水平显著变化。P45 OllE 1的变化仅为 在肝脏中观察到，但在肝外组织中未观察到，表明可能存在 肝细胞生长因子在P45 OlIE 1调节中的作用合作 与Ravindranath博士，P45 OlIE 1在大脑中的存在及其诱导 慢性酒精饮料后的表现。我们还发现， P45 OlIE 1可被蛋白激酶C磷酸化，cAMP依赖性蛋白 激酶或钙调蛋白依赖性蛋白激酶。

We previously cloned and demonstrated four distinct types of regulation of P450llE1. During the past year, we demonstrated two additional mechanisms of P450llE1 regulation: translational activation of P45OllE1 by isoniazid and pyrazine; and pretranslational suppression of hepatic P45OllE1 during pregnancy. Specific translational induction of P45OllE1 by isoniazid and pyrazine was demonstrated. However, pyridazine and pyrimidine, two stereoisomers of pyrazine, did not activate P45OllE1, indicating a more inflexible structural requirement for P450llE1 mRNA translation into its protein. In contrast, pyrrole with five-membered ring structure reduced P45OllE1 activity resulting from rapid reversal (within 1 day) upon parturition were also demonstrated. Exogenously administered steroids (progesterone, estrogen, and thyroxine) and peptide growth factors (placental lactogen, prolactin, and growth hormone) did not cause significant changes in P45OllE1 level. The changes in P45OllE1 was only observed in liver but not in extrahepatic tissues, suggesting a potential role of hepatocyte growth factor in P45OllE1 regulation. In collaboration with Dr. Ravindranath, the presence of P45OllE1 in brain and its induction after chronic ethanol drinking were demonstrated. We also showed that P45OllE1 can be phosphorylated by protein kinase C, cAMP dependent protein kinase or calmodulin-dependent protein kinase.