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

Arch Toxicol. 2005 Apr;79(4):192-5. doi: 10.1007/s00204-004-0630-8. Epub 2005 Jan 15.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aldehyde Oxidoreductases / genetics*
  • Animals
  • Aryl Hydrocarbon Hydroxylases / biosynthesis
  • Aryl Hydrocarbon Hydroxylases / genetics
  • Central Nervous System Depressants / pharmacology*
  • Cytochrome P-450 CYP2B1 / biosynthesis
  • Cytochrome P-450 CYP2B1 / genetics
  • Cytochrome P-450 CYP2E1 / biosynthesis
  • Cytochrome P-450 CYP2E1 / genetics
  • Cytochrome P-450 Enzyme System / biosynthesis*
  • Cytochrome P-450 Enzyme System / genetics
  • Ethanol / pharmacology*
  • Gene Expression Regulation, Enzymologic / drug effects
  • Genotype
  • Immunoblotting
  • Liver / drug effects
  • Liver / enzymology*
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Microsomes, Liver / drug effects
  • Microsomes, Liver / enzymology
  • Pilot Projects

Substances

  • Central Nervous System Depressants
  • Ethanol
  • Cytochrome P-450 Enzyme System
  • Cytochrome P-450 CYP2E1
  • Aryl Hydrocarbon Hydroxylases
  • Cytochrome P-450 CYP2B1
  • cytochrome P-450 CYP4B1
  • Aldehyde Oxidoreductases
  • aldehyde dehydrogenase (NAD(P)+)