Effect of chloroquine and leupeptin on intracellular accumulation of amyloid-beta (Aβ) 1-42 peptide in a murine N9 microglial cell line

被引:28
作者
Chua, T
Tran, T
Yang, F
Beech, W
Cole, GM
Frautschy, SA [1 ]
机构
[1] Univ Calif Los Angeles, Dept Med, Los Angeles, CA 90024 USA
[2] Sepulveda VAMC, Ctr Geriatr Res Educ & Clin, Sepulveda, CA 91343 USA
[3] Univ Calif Los Angeles, Dept Neurol, Los Angeles, CA 90024 USA
关键词
Alzheimer's disease; beta A4 amyloid; lysosome; microglia; chloroquine; leupeptin;
D O I
10.1016/S0014-5793(98)01161-2
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
Murine N9 microglia accumulated A beta from media containing 0.67 mu M A beta within 6 h. In N9 and in primary rat microglia, chloroquine, which disrupts lysosomal pH, increased A beta-induced accumulation of A beta, particularly A beta 1-2. Leupeptin similarly enhanced A beta accumulation. The scavenger receptor antagonist fucoidan did not affect acute chloroquine-dependent A beta 1-42 accumulation, demonstrating uptake of non-aggregated A beta, After prolonged incubations, chloroquine enhanced A beta multimer (8-12 kDa) accumulation, an effect inhibited by fucoidan. Disruptions of the lysosomal system enhance A beta and its multimer formation. Despite negligible effects of fucoidan on initial A beta uptake, chronic exposure inhibits multimer accumulation, demonstrating a role for scavenger receptor in multimer accumulation. (C) 1998 Federation of European Biochemical Societies.
引用
收藏
页码:439 / 444
页数:6
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