Single-dose ethanol administration downregulates expression of cytochrome p450 2E1 mRNA in aldehyde dehydrogenase 2 knockout mice

Nov 6, 2007Alcohol (Fayetteville, N.Y.)

One dose of alcohol lowers a liver enzyme gene in mice lacking a key aldehyde-processing enzyme

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Abstract

Acetaldehyde metabolism is significantly impaired in individuals with the *ALDH22** polymorphism.

ALDH2*2 is common among individuals of East Asian descent and affects ethanol metabolism.
CYP2E1, a cytochrome P450 enzyme, is linked to increased oxidative stress and carcinogen activation.
Ethanol administration influences CYP2E1 gene expression in liver tissue.
In mice with normal ALDH2, CYP2E1 mRNA levels increased 12 hours after ethanol administration.
Mice lacking functional ALDH2 showed a significant decrease in CYP2E1 mRNA levels after the same treatment.
These findings indicate that inactive ALDH2 may downregulate CYP2E1 expression following ethanol exposure.

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The polymorphism of aldehyde dehydrogenase 2 (ALDH2), denoted ALDH22, is very common in East Asian origin. Acetaldehyde, an intermediate metabolite of ethanol, is metabolized very slowly in people with ALDH22 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 5 g/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.

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Single-dose ethanol administration downregulates expression of cytochrome p450 2E1 mRNA in aldehyde dehydrogenase 2 knockout mice

Abstract

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