Expression levels of hepatic cytochrome P450 enzymes in Aldh2-deficient mice following ethanol exposure: a pilot study

Jan 18, 2005Archives of toxicology

Liver enzyme levels after alcohol exposure in mice lacking Aldh2

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Abstract

CYP2E1, 2B1/2, and 4B1 enzyme levels increased by 2.61, 1.88, and 2.01 times in Aldh2 +/+ mice after ethanol exposure.

Ethanol exposure elevated CYP2E1, 2B1/2, and 4B1 protein levels in Aldh2 +/+ mice compared to their unexposed controls.
In Aldh2 -/- mice, CYP2E1, 2B1/2, and 4B1 expression levels were increased by 1.99, 1.05, and 1.33 times after ethanol treatment, respectively.
Aldh2 -/- mice exhibited significantly higher levels of CYP2E1 (4.19 times), 2B1/2 (2.89 times), and 4B1 (1.53 times) compared to Aldh2 +/+ mice without ethanol treatment.
These results indicate a potential role of CYP2E1, 2B1/2, and 4B1 in ethanol metabolism.
Individuals lacking Aldh2 may have higher levels of these enzymes compared to those with the Aldh2 gene.

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We determined expression levels of hepatic cytochrome P450 (CYP) 2E1, 2B1/2 and 4B1 enzymes in aldehyde dehydrogenase 2 (Aldh2) +/+ and Aldh2 -/- mice by immunoblotting assay following subchronic ethanol exposure for eight days. Using ethanol exposure, the protein expression levels of CYP2E1, 2B1/2 and 4B1 in Aldh2 +/+ mice were increased by factors of 2.61, 1.88 and 2.01 compared with Aldh2 +/+ mice that were not exposed to ethanol, respectively. On the other hand, in the Aldh2 -/- mice, CYP2E1, 2B1/2 and 4B1 protein expression levels after ethanol treatment were shown to be 1.99, 1.05 and 1.33 greater than those of Aldh2 -/- control mice, respectively. We also found an interesting fact in the present study; the Aldh2 -/- mice were shown to have higher CYP2E1 (by a factor of 4.19), 2B1/2 (by a factor of 2.89) and 4B1 (by a factor of 1.53) protein expression levels than Aldh2 +/+ mice despite the lack of ethanol treatment. These results suggest that CYP2E1, 2B1/2 and 4B1 play some role in ethanol metabolism and that Aldh2-deficient individuals may have higher levels of CYP2E1, 2B1/2 and 4B1 enzymes compared to Aldh2 wild-type individuals.

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Expression levels of hepatic cytochrome P450 enzymes in Aldh2-deficient mice following ethanol exposure: a pilot study

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