Aryl hydrocarbon receptor-dependent upregulation of Cyp1b1 by TCDD and diesel exhaust particles in rat brain microvessels

Fluids and Barriers of the CNS

Xavier Declèves³  Björn Bauer¹  Jean-Michel Scherrmann³  Salah Yousif³  Xavier Coumoul²  Sophie Potin³  Anika MS Hartz¹  Aude Jacob³ 

[1] Brain Barriers Research Center, College of Pharmacy, University of Minnesota, Duluth, USA;INSERM UMR-S747, Toxicologie, pharmacologie et signalisation cellulaire, Université Paris Descartes, 45 rue des Saints-Pères 75006 Paris, France;INSERM U705, Neuropsychopharmacologie des addictions, Paris, France

关键词: brain microvessels;    diesel exhaust particles;    TCDD;    Cyp1b1;    Aryl hydrocarbon Receptor;   

Others  :  807402
DOI  :  10.1186/2045-8118-8-23

 received in 2011-05-18, accepted in 2011-08-25,  发布年份 2011

【 摘 要 】

Background

AhR activates the transcription of several target genes including CYP1B1. Recently, we showed CYP1B1 as the major cytochrome P450 (CYP) enzyme expressed in human brain microvessels. Here, we studied the effect of AhR activation by environmental pollutants on the expression of Cyp1b1 in rat brain microvessels.

Methods

Expression of AhR and Cyp1b1 was detected in isolated rat brain microvessels. AhR was immunovisualised in brain microvessel endothelial cells. The effect of AhR ligands on Cyp1b1 expression was studied using isolated brain microvessels after ex vivo and/or in vivo exposure to TCDD, heavy hydrocarbons containing diesel exhaust particles (DEP) or Δ⁹-tetrahydrocannabinol (Δ⁹-THC).

Results

After ex vivo exposure to TCDD (a highly potent AhR ligand) for 3 h, Cyp1b1 expression was significantly increased by 2.3-fold in brain microvessels. A single i.p. dose of TCDD also increased Cyp1b1 transcripts (22-fold) and Cyp1b1 protein (2-fold) in rat brain microvessels at 72 h after TCDD. Likewise, DEP treatment (in vivo and ex vivo) strongly induced Cyp1b1 protein in brain microvessels. DEP-mediated Cyp1b1 induction was inhibited by actinomycin D, cycloheximide, or by an AhR antagonist. In contrast, a sub-chronic in vivo treatment with Δ⁹-THC once daily for 7 seven days had no effect on Cyp1b1 expression

Conclusions

Our results show that TCDD and DEP strongly induced Cyp1b1 in rat brain microvessels, likely through AhR activation.

【 授权许可】

   
2011 Jacob et al; licensee BioMed Central Ltd.

【 图 表 】

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