Expression of CYP2E1 and CYP2U1 proteins in amygdala and prefrontal cortex: influence of alcoholism and smoking

Toselli, Francesca, Depaz, Iris M. Booth, Worrall, Simon, Etheridge, Naomi, Dodd, Peter R., Wilce, Peter A. and Gillam, Elizabeth M. J. (2015) Expression of CYP2E1 and CYP2U1 proteins in amygdala and prefrontal cortex: influence of alcoholism and smoking. Alcoholism: Clinical and Experimental Research, 39 5: 790-797. doi:10.1111/acer.12697

Author Toselli, Francesca
Depaz, Iris M. Booth
Worrall, Simon
Etheridge, Naomi
Dodd, Peter R.
Wilce, Peter A.
Gillam, Elizabeth M. J.
Title Expression of CYP2E1 and CYP2U1 proteins in amygdala and prefrontal cortex: influence of alcoholism and smoking
Journal name Alcoholism: Clinical and Experimental Research   Check publisher's open access policy
ISSN 1530-0277
Publication date 2015-05
Sub-type Article (original research)
DOI 10.1111/acer.12697
Open Access Status Not Open Access
Volume 39
Issue 5
Start page 790
End page 797
Total pages 8
Place of publication Hoboken, NJ, United States
Publisher Wiley-Blackwell Publishing
Collection year 2016
Language eng
Formatted abstract
Background:  The tissue-specific expression of cytochrome P450 enzymes (CYP, P450) in the human brain may influence the therapeutic response to, and side effects of, neuroactive drugs including alcohol. However, the distribution of many P450s, especially poorly characterized CYP2 forms, within specific regions of the brain remains obscure, partly due to the paucity of available tissue and difficulty in discriminating between related P450s with available antibodies.

Methods:  In this study, we analyzed the expression of CYP2A6, CYP2B6, CYP2D6, CYP2E1, CYP2J2, CYP2S1, CYP2U1, and CYP2W1 proteins in human prefrontal cortex (PFC) and amygdala (AMG) by immunoblotting with antibodies for which the P450 form specificity had been enhanced by affinity purification. These brain regions were selected as they mediate the addictive effects of cigarette smoking and alcohol consumption, substances known to modulate P450 expression in other tissues. PFC and AMG samples from alcoholic smokers, alcoholic nonsmokers, nonalcoholic smokers, and nonalcoholic nonsmokers were studied to assess the effect of alcohol use and smoking on the expression of these proteins.

Results:  Of the P450s studied, CYP2E1 and CYP2U1 were expressed in all samples analyzed (n = 26 and 22 for CYP2E1 and CYP2U1, respectively), and elevated in alcoholics. CYP2U1 expression was also slightly increased in smokers. Expression of both P450s was increased in AMG compared to PFC of the same individuals.

Conclusions:  This is the first report of CYP2E1 and CYP2U1 protein expression in human AMG. Our results suggest that CYP2U1 expression may be modulated by alcohol and tobacco, with potential consequent effects on the metabolism of drugs and endogenous chemicals by this enzyme.
Keyword Amygdala
Cytochrome P450
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: Official 2016 Collection
School of Biomedical Sciences Publications
School of Chemistry and Molecular Biosciences
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Citation counts: TR Web of Science Citation Count  Cited 2 times in Thomson Reuters Web of Science Article | Citations
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