Single-dose ethanol administration downregulates expression of cytochrome p450 2E1 mRNA in aldehyde dehydrogenase 2 knockout mice.
Single-dose ethanol administration downregulates expression of cytochrome p450 2E1 mRNA in aldehyde dehydrogenase 2 knockout mice.
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DOI：
10.1016/j.alcohol.2007.08.002
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发表时间：
2007-12
期刊：
影响因子：
2.3
通讯作者：
A. Matsumoto;T. Kawamoto;Mikako Horita;Tatsuya Takahashi;T. Isse;T. Oyama;M. Ichiba
中科院分区：
文献类型：
--
作者：
A. Matsumoto;T. Kawamoto;Mikako Horita;Tatsuya Takahashi;T. Isse;T. Oyama;M. Ichiba
乙醛脱氢酶2（aldehyde dehydrogenase 2，ALDH 2）基因多态性在东亚人群中非常普遍。乙醛是乙醇的中间代谢物，在ALDH 2 *2患者中代谢非常缓慢，因为突变的ALDH 2蛋白缺乏乙醛代谢的活性。另一方面，已经确定细胞色素P450酶之一CYP 2 E1是致癌物的活化剂（例如，亚硝胺）和氧化应激的发生器，并且显示CYP 2 E1通过基因转录调节被乙醇诱导。在本研究中，为了研究ALDH 2多态性对肝组织中CYP 2 E1转录调节的影响，Aldh 2 +/+和Aldh 2 −/−小鼠口服5g/kg体重的乙醇，然后分析肝组织中CYP 2 E1 mRNA的水平。乙醇给药后12 h，Aldh 2 +/+小鼠的CYP 2 E1 mRNA水平有高于0 h组的趋势，而Aldh 2 −/−小鼠的CYP 2 E1 mRNA水平显著低于0 h组。这些结果表明，单剂量乙醇管理下调细胞色素p450 2 E1 mRNA的表达，在无活性ALDH 2的存在。
The polymorphism of aldehyde dehydrogenase 2 (ALDH2), denoted ALDH2*2, is very common in East Asian origin. Acetaldehyde, an intermediate metabolite of ethanol, is metabolized very slowly in people with ALDH2*2 because the mutant ALDH2 protein lacks the activity of acetaldehyde metabolism. On the other hand, it is well established that one of the cytochrome P450 enzymes, CYP2E1, is an activator of carcinogens (e.g., nitorosamines) and a generator of oxidative stress, and it is shown that CYP2E1 was induced by ethanol via gene transcriptional regulation. In the present study, to examine the consequences of ALDH2 polymorphism on transcriptional regulation of CYP2E1 in liver tissue, Aldh2+/+ and Aldh2−/− mice were orally administered 5g/kg body weight of ethanol and the levels of CYP2E1 mRNA in liver tissue then analyzed. The level of CYP2E1 mRNA 12h after the ethanol administration tended to be higher than the 0-h group in Aldh2+/+ mice, however, it was significantly lower than the 0-h group in Aldh2−/− mice. These findings suggest that single-dose ethanol administration downregulates the expression of cytochrome p450 2E1 mRNA in the presence of inactive ALDH2.