Tissue-distribution of aldehyde dehydrogenase 2 and effects of the ALDH2 gene-disruption on the expression of enzymes involved in alcohol metabolism
Tissue-distribution of aldehyde dehydrogenase 2 and effects of the ALDH2 gene-disruption on the expression of enzymes involved in alcohol metabolism
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DOI：
10.2741/1589
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发表时间：
2005-01-01
影响因子：
3.1
通讯作者：
Kawamoto, T
中科院分区：
文献类型：
--
作者：
Oyama, T;Isse, T;Kawamoto, T
在酒精代谢中，乙醛是一种可能导致细胞和DNA损伤的高活性中间体，在线粒体乙醛脱氢酶ALDH2的作用下转化为乙酸酯。虽然摄入的大部分酒精在肝脏中被消除，但乙醇在上消化道的首过代谢对预防和管理与酒精相关的胃肠道疾病也很重要。然而，ALDH2在小鼠体内的组织分布研究很少。因此，在本研究中，我们用免疫组织化学方法研究了ALDH2以及Aldh1、Cyp1a1、Cyp2e1和Cyp4b1在野生型和ALDH2缺失小鼠体内的组织分布。还检查了人的肝脏和食道组织。在小鼠的肝、肺、心、肾、睾丸、食道、胃、结肠和胰腺中检测到ALDH2蛋白，表明ALDH2在小鼠中的组织分布与人类相似。因此，ALDH2基因缺失小鼠可能是研究酒精代谢及相关疾病的有用模型动物。Western印迹分析显示，与野生型相比，ALDH2缺失小鼠肝脏中的CYP2e1表达水平增加，而Aldh1、Cyp1a1和Cyp4b1的表达水平没有明显差异。这一结果提示ALDH2的代谢物S可能下调了细胞色素P450-2E_1基因的表达。
In alcohol metabolism, acetaldehyde, a highly reactive intermediate that may cause cellular and DNA damages, is converted to acetate by mitochondrial aldehyde dehydrogenase ALDH2. Although the majority of ingested alcohol is eliminated in the liver, the first-pass metabolism of ethanol in the upper digestive tract is also important for prevention and management of ethanol-related gastrointestinal diseases. However, the tissue-distribution of Aldh2 in mice has been poorly investigated. In this study, therefore, we investigated the tissue-distribution of Aldh2 as well as Aldh1, Cyp1a1, Cyp2e1, and Cyp4b1 in wild type and Aldh2-null mice by immuno-histochemical analysis. The human liver and esophageal tissues were also examined. In mice, the Aldh2 protein was detected in the liver, lung, heart, kidney, testis, esophagus, stomach, colon, and pancreas, suggesting that the tissue-distribution of Aldh2 in mice is similar to that in humans. Therefore, Aldh2-null mice may be useful model animals for the investigation of alcohol metabolism and related diseases. Compared with the wild type, the expression level of Cyp2e1 was increased in the liver from Aldh2-null mice based on Western blot analysis, whereas the levels of Aldh1, Cyp1a1, and Cyp4b1 were indistinguishable. This observation suggests that a metabolite(s) of Aldh2 might down-regulate the expression of Cyp2e1 gene.