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.
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.
authors.affiliation: a School of Chemistry and Molecular Biosciences, The University of Queensland , St. Lucia, Brisbane , Australia and.|b INSERM UMR-S1147, Paris Descartes University , Sorbonne Paris Cité, Paris , France.
authors.forename: Francesca
authors.initials: F
authors.lastname: Toselli
authors.affiliation: b INSERM UMR-S1147, Paris Descartes University , Sorbonne Paris Cité, Paris , France.
authors.forename: Isabelle
authors.initials: I
authors.lastname: de Waziers
authors.affiliation: b INSERM UMR-S1147, Paris Descartes University , Sorbonne Paris Cité, Paris , France.
authors.forename: Mary
authors.initials: M
authors.lastname: Dutheil
authors.affiliation: b INSERM UMR-S1147, Paris Descartes University , Sorbonne Paris Cité, Paris , France.
authors.forename: Marc
authors.initials: M
authors.lastname: Vincent
authors.affiliation: a School of Chemistry and Molecular Biosciences, The University of Queensland , St. Lucia, Brisbane , Australia and.
authors.forename: Peter A
authors.initials: PA
authors.lastname: Wilce
authors.affiliation: a School of Chemistry and Molecular Biosciences, The University of Queensland , St. Lucia, Brisbane , Australia and.
authors.forename: Peter R
authors.initials: PR
authors.lastname: Dodd
authors.affiliation: b INSERM UMR-S1147, Paris Descartes University , Sorbonne Paris Cité, Paris , France.
authors.forename: Philippe
authors.initials: P
authors.lastname: Beaune
authors.affiliation: b INSERM UMR-S1147, Paris Descartes University , Sorbonne Paris Cité, Paris , France.
authors.forename: Marie-Anne
authors.initials: MA
authors.lastname: Loriot
authors.affiliation: a School of Chemistry and Molecular Biosciences, The University of Queensland , St. Lucia, Brisbane , Australia and.
authors.forename: Elizabeth M J
authors.initials: EM
authors.lastname: Gillam
mesh_terms: D018528:ATP-Binding Cassette Transporters / Q000235:genetics*; D000325:Adrenodoxin / Q000096:biosynthesis / Q000235:genetics; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000437:Alcoholism / Q000201:enzymology / Q000235:genetics* / Q000378:metabolism; D000679:Amygdala / Q000201:enzymology / Q000378:metabolism*; D003577:Cytochrome P-450 Enzyme System / Q000235:genetics*; D005260:Female; D020869:Gene Expression Profiling; D005838:Genotype; D006801:Humans; D007527:Isoenzymes / Q000235:genetics; D008297:Male; D008875:Middle Aged; D017397:Prefrontal Cortex / Q000201:enzymology / Q000378:metabolism*; D012016:Reference Values; D012907:Smoking / Q000235:genetics* / Q000378:metabolism; D014157:Transcription Factors / Q000235:genetics*
chemical_list: D018528:ATP-Binding Cassette Transporters; D007527:Isoenzymes; D014157:Transcription Factors; D000325:Adrenodoxin; D003577:Cytochrome P-450 Enzyme System
keywords: ABC transporters; amygdala; cortex; cytochrome P450; smoking