Abstract |
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.
|
Authors | Shin-ichi Akanuma, Sumio Ohtsuki, Youko Doi, Masanori Tachikawa, Shingo Ito, Satoko Hori, Tomoko Asashima, Tadafumi Hashimoto, Kaoru Yamada, Kazumitsu Ueda, Takeshi Iwatsubo, Tetsuya Terasaki |
Journal | Neurochemistry international
(Neurochem Int)
Vol. 52
Issue 6
Pg. 956-61
(May 2008)
ISSN: 0197-0186 [Print] England |
PMID | 18201804
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
|
Chemical References |
- ABCA1 protein, human
- ATP Binding Cassette Transporter 1
- ATP-Binding Cassette Transporters
- Amyloid beta-Peptides
- Apolipoprotein A-I
- Peptide Fragments
- amyloid beta-protein (1-40)
|
Topics |
- ATP Binding Cassette Transporter 1
- ATP-Binding Cassette Transporters
(genetics)
- Amyloid beta-Peptides
(metabolism, pharmacology)
- Animals
- Apolipoprotein A-I
(metabolism)
- Biological Transport, Active
(genetics)
- Blood-Brain Barrier
(drug effects, metabolism)
- Brain
(blood supply, metabolism)
- Cell Line
- Cerebral Arteries
(metabolism)
- Endothelial Cells
(drug effects, metabolism)
- Humans
- Mice
- Mice, Knockout
- Microinjections
- Peptide Fragments
(metabolism, pharmacology)
|