ABC transporters, cytochromes P450 and their main transcription factors: expression at the human blood-brain barrier
ABC transporters, cytochromes P450 and their main transcription factors: expression at the human blood-brain barrier
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DOI：
10.1111/j.1471-4159.2008.05720.x
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发表时间：
2008-12-01
影响因子：
4.7
通讯作者：
Decleves, Xavier
中科院分区：
文献类型：
--
作者：
Dauchy, Sandrine;Dutheil, Fabien;Decleves, Xavier
我们已经建立了成人血脑屏障（BBB）的ATP结合盒（ABC）转运蛋白和细胞色素P450（CYP）编码基因的表达模式，使用分离的脑微血管和皮质活检癫痫或胶质瘤患者。微泡突触素（神经元）和神经胶质抗原2（NG 2）（周细胞）。ABCG 2 [乳腺癌耐药蛋白（BCRP）]和ABCB 1（MDR 1）是微血管中表达的主要ABC转运蛋白基因，微血管中ABCG 2和ABCB 1的表达量是皮质的20倍和25倍。CYP 1B 1亚型占微血管中检测到的所有CYP基因的80%以上。CYP 1B 1在微血管中的表达是在皮质中的14倍，表明CYP 1B 1主要在血脑屏障表达。Western blotting法检测微血管中P-糖蛋白（ABCB 1）、BCRP（ABCG 2）和CYP 1B 1蛋白的表达。研究了三种转录因子[甾烷异生素受体（PXR）、组成型雄烷受体（CAR）和芳烃受体（AhR）]基因的表达。参与CYP 1B 1表达调控的AhR基因在脑微血管中高度表达，而PXR和CAR基因几乎未检测到。ABC和CYP基因在人血脑屏障中表达的这种详细模式为理解其底物如何进入大脑提供了有用的信息。
We have established the expression patterns of the genes encoding ATP-binding cassette (ABC) transporters and cytochromes P450 (CYPs) at the adult human blood-brain barrier (BBB) using isolated brain microvessels and cortex biopsies from patients with epilepsia or glioma. Microves synaptophysin (neurons) and neuron-glial antigen 2 (NG2) (pericytes). ABCG2 [breast cancer resistance protein (BCRP)] and ABCB1 (MDR1) were the main ABC transporter genes expressed in microvessels, with 20 times more ABCG2 and 25 times more ABCB1 in microvessels than in the cortex. The CYP1B1 isoform represented over 80% of all the CYPs genes detected in microvessels. There were 14 times more CYP1B1 in microvessels than in the cortex, showing that CYP1B1 is mainly expressed at the BBB. p-glycoprotein (ABCB1), BCRP (ABCG2) and CYP1B1 proteins were found in microvessels by western blotting. The expression of genes encoding three transcription factors [pregnane xenobiotic receptor (PXR), constitutive androstane receptor (CAR), aryl hydrocarbon receptor (AhR)] was also investigated. The AhR gene, involved in the regulation of CYP1B1 expression, was highly expressed in brain microvessels, whereas PXR and CAR genes were almost undetected. This detailed pattern of ABC and CYPs gene expression at the human BBB provides useful information for understanding how their substrates enter the brain.