TY - JOUR
T1 - Expression of nuclear receptor mRNA and liver X receptor-mediated regulation of ABC transporter A1 at rat blood-brain barrier
AU - Akanuma, Shin ichi
AU - Hori, Satoko
AU - Ohtsuki, Sumio
AU - Fujiyoshi, Masachika
AU - Terasaki, Tetsuya
N1 - Funding Information:
We thank Ms. N. Funayama for secretarial assistance. This study was supported in part by a Grant-in-Aid for Scientific Research on Priority Areas (17081002) from the Ministry of Education, Culture, Sports, Science and Technology of Japan, a 21st Century Center of Excellence (COE) Program Grant from the Japan Society for the Promotion of Sciences. It was also supported in part by the Industrial Technology Research Grant Program from New Energy and the Industrial Technology Development Organization (NEDO) of Japan.
PY - 2008/3
Y1 - 2008/3
N2 - 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-BBB13). RT-PCR analysis revealed that liver X receptor α and β, retinoid X receptor α and β and peroxisome proliferator-activating receptor α and β mRNAs were expressed in the rat brain capillary endothelial cells and TR-BBB cells. In contrast, pregnane X receptor, farnesoid X receptor and constitutive androstane receptor were not detected. Furthermore, treatment with a liver X receptor agonist increased the ABCA1 mRNA level in TR-BBB13 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-BBB13 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.
AB - 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-BBB13). RT-PCR analysis revealed that liver X receptor α and β, retinoid X receptor α and β and peroxisome proliferator-activating receptor α and β mRNAs were expressed in the rat brain capillary endothelial cells and TR-BBB cells. In contrast, pregnane X receptor, farnesoid X receptor and constitutive androstane receptor were not detected. Furthermore, treatment with a liver X receptor agonist increased the ABCA1 mRNA level in TR-BBB13 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-BBB13 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.
KW - ABC transporter
KW - Blood-brain barrier
KW - Brain capillary endothelial cell
KW - LXR
KW - Nuclear receptor
KW - PPAR
KW - PXR
UR - http://www.scopus.com/inward/record.url?scp=38349098471&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=38349098471&partnerID=8YFLogxK
U2 - 10.1016/j.neuint.2007.08.012
DO - 10.1016/j.neuint.2007.08.012
M3 - Article
C2 - 17919779
AN - SCOPUS:38349098471
SN - 0197-0186
VL - 52
SP - 669
EP - 674
JO - Neurochemistry International
JF - Neurochemistry International
IS - 4-5
ER -