Gene expression profiling of cytochromes P450, ABC transporters and their principal transcription factors in the amygdala and prefrontal cortex of alcoholics, smokers and drug-free controls by qRT-PCR

Toselli, Francesca, de Waziers, Isabelle, Dutheil, Mary, Vincent, Marc, Wilce, Peter A., Dodd, Peter R., Beaune, Philippe, Loriot, Marie-Anne and Gillam, Elizabeth M. J. (2015) Gene expression profiling of cytochromes P450, ABC transporters and their principal transcription factors in the amygdala and prefrontal cortex of alcoholics, smokers and drug-free controls by qRT-PCR. Xenobiotica, 45 12: 1129-1137. doi:10.3109/00498254.2015.1040102


Author Toselli, Francesca
de Waziers, Isabelle
Dutheil, Mary
Vincent, Marc
Wilce, Peter A.
Dodd, Peter R.
Beaune, Philippe
Loriot, Marie-Anne
Gillam, Elizabeth M. J.
Title Gene expression profiling of cytochromes P450, ABC transporters and their principal transcription factors in the amygdala and prefrontal cortex of alcoholics, smokers and drug-free controls by qRT-PCR
Journal name Xenobiotica   Check publisher's open access policy
ISSN 0049-8254
1366-5928
Publication date 2015-06-01
Year available 2015
Sub-type Article (original research)
DOI 10.3109/00498254.2015.1040102
Open Access Status Not yet assessed
Volume 45
Issue 12
Start page 1129
End page 1137
Total pages 9
Place of publication London, United Kingdom
Publisher Informa Healthcare
Language eng
Subject 1303 Biochemistry
3005 Toxicology
3004 Pharmacology
2307 Health, Toxicology and Mutagenesis
Abstract 1. Ethanol consumption and smoking alter the expression of certain drug-metabolizing enzymes and transporters, potentially influencing the tissue-specific effects of xenobiotics.
Formatted abstract
1. Ethanol consumption and smoking alter the expression of certain drug-metabolizing enzymes and transporters, potentially influencing the tissue-specific effects of xenobiotics.

2. Amygdala (AMG) and prefrontal cortex (PFC) are brain regions that modulate the effects of alcohol and smoking, yet little is known about the expression of cytochrome P450 enzymes (P450s) and ATP-binding cassette (ABC) transporters in these tissues.

3. Here, we describe the first study on the expression of 19 P450s, their redox partners, three ABC transporters and four related transcription factors in the AMG and PFC of smokers and alcoholics by quantitative RT-PCR.

4. CYP1A1, CYP1B1, CYP2B6, CYP2C8, CYP2C18, CYP2D6, CYP2E1, CYP2J2, CYP2S1, CYP2U1, CYP4X1, CYP46, adrenodoxin and NADPH-P450 reductase, ABCB1, ABCG2, ABCA1, and transcription factors aryl hydrocarbon receptor AhR and proliferator-activated receptor α were quantified in both areas. CYP2A6, CYP2C9, CYP2C19, CYP3A4, CYP3A5, adrenodoxin reductase and the nuclear receptors pregnane X receptor and constitutive androstane receptor were detected but below the limit of quantification. CYP1A2 and CYP2W1 were not detected.

5. Adrenodoxin expression was elevated in all case groups over controls, and smokers showed a trend toward higher CYP1A1 and CYP1B1 expression.

6. Our study shows that most xenobiotic-metabolizing P450s and associated redox partners, transporters and transcription factors are expressed in human AMG and PFC.
Keyword Abc Transporters
Amygdala
Cortex
Cytochrome P450
Smoking
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: Official 2016 Collection
School of Chemistry and Molecular Biosciences
 
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Created: Fri, 26 Jun 2015, 20:45:46 EST by Mrs Louise Nimwegen on behalf of School of Chemistry & Molecular Biosciences