Expression of nuclear receptor mRNA and liver X receptor-mediated regulation of ABC transporter A1 at rat blood-brain barrier

被引:40
作者
Akanuma, Shin-Ichi [1 ]
Hori, Satoko [1 ,2 ,3 ]
Ohtsuki, Sumio [1 ,2 ,3 ]
Fujiyoshi, Masachika [1 ]
Terasaki, Tetsuya [1 ,2 ,3 ]
机构
[1] Tohoku Univ, Div Membrane Transport & Drug Targeting, Grad Sch Pharmaceut Sci, Aoba Ku, Sendai, Miyagi 9808578, Japan
[2] Japan Sci & Technol Agcy, CREST, Tokyo, Japan
[3] Japan Sci & Technol Agcy, SORST, Tokyo, Japan
基金
日本学术振兴会;
关键词
ABC transporter; blood-brain barrier; brain capillary endothelial cell; nuclear receptor; LXR; PPAR; PXR;
D O I
10.1016/j.neuint.2007.08.012
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
The aim of the present study was to investigate the expression of nuclear receptor mRNA and regulation of the expression of ATP-binding cassette (ABC) transporters by nuclear receptor agonists in rat brain capillary endothelial cells, which form the blood-brain barrier, by using rat brain capillary fraction from 8-week-old rats and a conditionally immortalized brain capillary endothelial cell line (TR-BBB 13). RT-PCR analysis revealed that liver X receptor alpha and beta, retinoid X receptor alpha and beta and peroxisome proliferator-activating receptor alpha and beta mRNAs were expressed in the rat brain capillary endothelial cells and TR-BBB cells. In contrast, pregnane X receptor, famesoid X receptor and constitutive androstane receptor were not detected. Furthermore, treatment with a liver X receptor agonist increased the ABCA1 mRNA level in TR-BBB 13 cells, while ABCG2 mRNA expression was not affected. Treatment with a rat pregnane X receptor agonist did not affect the ABCB1 mRNA level in TR-BBB 13 cells. These results demonstrate that the rat blood-brain barrier has an expressional regulation mechanism via sterol-related nuclear receptor, and indicate that the blood-brain barrier in 8-week-old rats lacks ABCB1 regulation via pregnane X receptor. (C) 2007 Elsevier Ltd. All rights reserved.
引用
收藏
页码:669 / 674
页数:6
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