Aryl hydrocarbon receptor-dependent upregulation of Cyp1b1 by TCDD and diesel exhaust particles in rat brain microvessels. - Archive ouverte HAL Access content directly
Journal Articles Fluids and Barriers of the CNS Year : 2011

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

(1) , (2) , (1) , (3) , (1) , (1) , (4) , (1)
1
2
3
4

Abstract

ABSTRACT: 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 Delta9-tetrahydrocannabinol (Delta9-THC). RESULTS: After ex vivo exposure to TCDD (a highly potent AhR ligand) for 3h, 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 72h 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 Delta9-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.
Fichier principal
Vignette du fichier
2045-8118-8-23.pdf (506.77 Ko) Télécharger le fichier
Vignette du fichier
2045-8118-8-23.xml (79.05 Ko) Télécharger le fichier
Origin : Publisher files allowed on an open archive
Format : Other
Loading...

Dates and versions

inserm-00626715 , version 1 (26-09-2011)

Identifiers

Cite

Aude Jacob, Anika Hartz, Sophie Potin, Xavier Coumoul, Salah Yousif, et al.. Aryl hydrocarbon receptor-dependent upregulation of Cyp1b1 by TCDD and diesel exhaust particles in rat brain microvessels.. Fluids and Barriers of the CNS, 2011, 8 (1), pp.23. ⟨10.1186/2045-8118-8-23⟩. ⟨inserm-00626715⟩
381 View
208 Download

Altmetric

Share

Gmail Facebook Twitter LinkedIn More