Tissue-distribution of aldehyde dehydrogenase 2 and effects of the Aldh2 gene-disruption on the expression of enzymes involved in alcohol metabolism

Dec 1, 2004Frontiers in bioscience : a journal and virtual library

How ALDH2 enzyme is distributed in the body and how ALDH2 gene disruption affects alcohol-processing enzymes

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Abstract

Aldh2 protein was detected in the liver, lung, heart, kidney, testis, esophagus, stomach, colon, and pancreas of mice.

The tissue distribution of Aldh2 in mice is similar to that found in humans.
Aldh2-null mice may serve as valuable models for studying alcohol metabolism and related diseases.
Cyp2e1 expression levels were increased in the liver of Aldh2-null mice compared to wild type.
The expression levels of Aldh1, Cyp1a1, and Cyp4b1 were similar between Aldh2-null and wild type mice.
Aldh2 may influence the expression of Cyp2e1 by down-regulating its gene.

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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.

Tissue-distribution of aldehyde dehydrogenase 2 and effects of the Aldh2 gene-disruption on the expression of enzymes involved in alcohol metabolism

Abstract

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