Akanuma Shin-ichi, Ohtsuki Sumio, Doi Youko, Tachikawa Masanori, Ito Shingo, Hori Satoko, Asashima Tomoko, Hashimoto Tadafumi, Yamada Kaoru, Ueda Kazumitsu, Iwatsubo Takeshi, Terasaki Tetsuya
Division of Membrane Transport and Drug Targeting, Graduate School of Pharmaceutical Sciences, Tohoku University, Aoba, Aramaki, Aoba-ku, Sendai 980-8578, Japan.
Neurochem Int. 2008 May;52(6):956-61. doi: 10.1016/j.neuint.2007.12.002. Epub 2007 Dec 8.
ATP-binding cassette transporter A1 (ABCA1) mediates apolipoprotein-dependent cholesterol release from cellular membranes. Recent studies using ABCA1 knockout mice have demonstrated that ABCA1 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 ABCA1 affects the brain-to-blood efflux transport of human A beta(1-40)(hA beta(1-40)) at the BBB. The apparent uptake of [125I]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, [125I]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 ABCA1 does not directly transport hA beta(1-40) and a deficiency of ABCA1 does not attenuate the brain-to-blood efflux transport of hA beta(1-40) across the BBB.
ATP结合盒转运蛋白A1（ABCA1）介导细胞膜上载脂蛋白依赖性胆固醇的释放。最近使用ABCA1基因敲除小鼠的研究表明，ABCA1会影响大脑中β淀粉样肽（Aβ）的水平以及老年斑的形成。大脑中的Aβ（1-40）通过表达ABCA1的血脑屏障（BBB）从大脑清除进入循环血液。因此，在本研究中，我们研究了ABCA1是否会影响血脑屏障处人Aβ（1-40）（hAβ（1-40））从脑到血的外流转运。[125I]hAβ（1-40）在表达ABCA1的HEK293细胞中的表观摄取与在亲本HEK293细胞中的表观摄取没有显著差异。此外，即使存在作为胆固醇释放受体的载脂蛋白A-I时，表观摄取也没有受到显著影响。而且，在将[125I]hAβ（1-40）注入大脑60分钟后，ABCA1缺陷小鼠和野生型小鼠的[125I]hAβ（1-40）通过血脑屏障从脑内清除的情况没有显著差异。这些结果表明，ABCA1不会直接转运hAβ（1-40），并且ABCA1的缺乏不会减弱hAβ（1-40）通过血脑屏障从脑到血的外流转运。
