In:
Alcoholism: Clinical and Experimental Research, Wiley, Vol. 39, No. 5 ( 2015-05), p. 790-797
Abstract:
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 CYP 2 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 CYP 2A6, CYP 2B6, CYP 2D6, CYP 2E1, CYP 2J2, CYP 2S1, CYP 2U1, and CYP 2W1 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, CYP 2E1 and CYP 2U1 were expressed in all samples analyzed ( n = 26 and 22 for CYP 2E1 and CYP 2U1, respectively), and elevated in alcoholics. CYP 2U1 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 CYP 2E1 and CYP 2U1 protein expression in human AMG . Our results suggest that CYP 2U1 expression may be modulated by alcohol and tobacco, with potential consequent effects on the metabolism of drugs and endogenous chemicals by this enzyme.
Type of Medium:
Online Resource
ISSN:
0145-6008
,
1530-0277
DOI:
10.1111/acer.2015.39.issue-5
Language:
English
Publisher:
Wiley
Publication Date:
2015
detail.hit.zdb_id:
2046886-6
detail.hit.zdb_id:
3167872-5
SSG:
15,3
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