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Drug Metabolism and Disposition Fast Forward
First published on October 16, 2007; DOI: 10.1124/dmd.107.017228

0090-9556/08/3601-182-189$20.00
DMD 36:182-189, 2008

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Transcription Factor and Drug-Metabolizing Enzyme Gene Expression in Lymphocytes from Healthy Human Subjects

Gérard Siest, Elise Jeannesson, Jean-Brice Marteau, Anastasia Samara, Bérangère Marie, Michèle Pfister, and Sophie Visvikis-Siest

Equipe Institut National de la Santé et de la Recherche Médicale "Génétique Cardiovasculaire" CIC 9501, Faculté de Pharmacie, Université Henri Poincaré–Nancy I, Nancy, France

We aimed to measure simultaneously the expression of drug-metabolizing enzymes (DME) and transcription factors (TF) with high importance in cardiovascular physiopathology in lymphocytes from healthy subjects. RNA was isolated from peripheral blood mononuclear cells (PBMC) of 20 subjects from the Stanislas Cohort. We used a microarray approach to measure 16 DME and 13 TF. Cytochromes P450 (P450s), including CYP2C19, CYP2C9, CYP2J2, CYP2D6, CYP1A1, CYP4F2, CYP4A11, CYP2E1, CYP11B2, CYP2C18, and CYP2A6, were expressed in all the subjects. CYP3A4 and CYP3A5 were not expressed. Glutathione S-transferases (GST) were expressed, but GSTM1 was seen only in some subjects. Pregnane X receptor (PXR), myocyte enhancer factor 2, vitamin D receptor, liver X receptor (LXR)-{alpha}, aryl hydrocarbon receptor (AHR), T-cell factor 7, constitutive androstane receptor, and aryl hydrocarbon receptor nuclear translocator (ARNT) were expressed in the majority of the subjects. Glucocorticoid receptor, peroxisome proliferator-activated receptor (PPAR)-{gamma}, and LXRβ were expressed only in some individuals. PPAR{alpha} mRNA was found in one subject only, and farnesoid X-activated receptor was not expressed. In addition, we found significant correlations between the expression of AHR, ARNT, and CYP1A1 and between PXR and P450 involved in leukotriene metabolism (CYP2C, CYP4F2, CYP4A11, CYP2J2, and CYP11B2). We describe here for the first time the presence of the majority of TF and DME in PBMC of healthy subjects without previous induction. The expression of these genes in lymphocytes could be a useful tool for further studying the physiological and pathological variations of DME and TF related to environment, to drug intake, and to cardiovascular metabolic cycles.

Address correspondence to: Gérard Siest, Faculté de Pharmacie, Equipe Inserm "Génétique Cardiovasculaire" CIC 9501, 30 rue Lionnois, 54000 Nancy, France. E-mail: gerard.siest{at}pharma.uhp-nancy.fr






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