ATP-binding cassette transporter A1 (ABCA1) deficiency does not attenuate the brain-to-blood efflux transport of human amyloid-β peptide (1-40) at the blood-brain barrier

被引：42

作者：

Akanuma, Shin-Ichi ^{[1
]}

Ohtsuki, Sumio ^{[1
]}

Doi, Youko ^{[1
]}

Tachikawa, Masanori ^{[1
]}

Ito, Shingo ^{[1
]}

Hori, Satoko ^{[1
]}

Asashima, Tomoko ^{[1
]}

Hashimoto, Tadafumi ^{[2
]}

Yamada, Kaoru ^{[2
]}

Ueda, Kazumitsu ^{[3
]}

Iwatsubo, Takeshi ^{[2
]}

Terasaki, Tetsuya ^{[1
]}

机构：

[1] Tohoku Univ, Grad Sch Pharmaceut Sci, Div Membrane Transport & Drug Targeting, Aoba Ku, Sendai, Miyagi 9808578, Japan

[2] Univ Tokyo, Dept Neuropathol & Neurosci, Grad Sch Pharmaceut Sci, Bunkyo Ku, Tokyo 1130033, Japan

[3] Kyoto Univ, Lab Cellular Biochem, Div Appl Life Sci, Grad Sch Agr, Kyoto 6068502, Japan

来源：

NEUROCHEMISTRY INTERNATIONAL | 2008年 / 52卷 / 06期

基金：

日本学术振兴会;

关键词：

Alzheimer's disease; ATP-binding cassette transporter; mouse blood-brain barrier; amyloid-beta peptide (1-40); ABCA1; mouse brain efflux index study; ABCA1 knockout mouse; LXR;

D O I：

10.1016/j.neuint.2007.12.002

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：

ATP-binding cassette transporter A1 (ABCA1) mediates apolipoprotein-dependent cholesterol release from cellular membranes. Recent studies using ABCA1 knockout mice have demonstrated that ABCAI affects amyloid-beta peptide (A beta) levels in the brain and the production of senile plaque. Cerebral A beta(1-40) was eliminated from the brain to the circulating blood via the blood-brain barrier (BBB), which expresses ABCA1. Therefore, in the present study, we examined whether ABCAI affects the brain-to-blood efflux transport of human A beta(1-40)(hA beta(1-40)) at the BBB. The apparent uptake of [I-125]hA beta(1-40) into ABCA1-expressing HEK293 cells was not significantly different from that into parental HEK293 cells. In addition, the apparent uptake was not significantly affected even in the presence of apolipoprotein A-I as a cholesterol release acceptor. Moreover, [I-125]hA beta(1-40) elimination from mouse brain across the BBB was not significantly different between ABCA1-deficient and wild-type mice 60 min after its administration into the cerebrum. These results suggest that ABCAI does not directly transport hA beta(1-40) and a deficiency of ABCAI does not attenuate the brain-to-blood efflux transport of hA beta(1-40) across the BBB. (C) 2007 Elsevier Ltd. All rights reserved.

引用

页码：956 / 961

页数：6

共 33 条

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