Aryl hydrocarbon receptor-dependent upregulation of Cyp1b1 by TCDD and diesel exhaust particles in rat brain microvessels
Aryl hydrocarbon receptor-dependent upregulation of Cyp1b1 by TCDD and diesel exhaust particles in rat brain microvessels
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DOI：
10.1186/2045-8118-8-23
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发表时间：
2011-08-25
影响因子：
7.3
通讯作者：
Decleves, Xavier
中科院分区：
文献类型：
--
作者：
Jacob, Aude;Hartz, Anika M. S.;Decleves, Xavier
背景：AhR激活包括CYP 1B 1在内的几种靶基因的转录。最近，我们发现CYP 1B 1是人脑微血管中表达的主要细胞色素P450（CYP）酶。本研究旨在探讨环境污染物激活AhR对大鼠脑微血管Cyp 1b 1表达的影响。AhR在脑微血管内皮细胞中免疫可视化。采用离体和/或体内暴露于TCDD、含柴油机尾气颗粒的重烃（DEP）或Delta（9）-四氢大麻酚（Delta（9）-THC）后的脑微血管，研究AhR配体对Cyp 1b 1表达的影响。一个单一的ip剂量的TCDD也增加Cyp 1b 1转录（22倍）和Cyp 1b 1蛋白（2倍）在大鼠脑微血管在72小时后TCDD。同样，DEP治疗（体内和体外）强烈诱导Cyp 1b 1蛋白在脑微血管。DEP介导的Cyp 1b 1诱导抑制放线菌素D，放线菌酮，或AhR拮抗剂。相反，用Delta（9）-THC每天一次亚慢性体内处理7天对Cyp 1b 1表达没有影响。结论：我们的结果表明，TCDD和DEP强烈诱导大鼠脑微血管中Cyp 1b 1的表达，可能通过AhR激活。
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 Delta(9)-tetrahydrocannabinol (Delta(9)-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 Delta(9)-THC once daily for 7 seven days had no effect on Cyp1b1 expressionConclusions: Our results show that TCDD and DEP strongly induced Cyp1b1 in rat brain microvessels, likely through AhR activation.