β-淀粉样肽通过PI3激酶/Akt信号通路在培养的Ra2小胶质细胞中诱导细胞增殖和巨噬细胞集落刺激因子表达。

Amyloid-beta peptides induce cell proliferation and macrophage colony-stimulating factor expression via the PI3-kinase/Akt pathway in cultured Ra2 microglial cells.

作者信息

Ito Sachiko, Sawada Makoto, Haneda Masataka, Fujii Satoshi, Oh-Hashi Kentaro, Kiuchi Kazutoshi, Takahashi Masahide, Isobe Ken-Ichi

机构信息

Department of Basic Gerontology, National Institute for Longevity Sciences, 36-3 Gengo, Morioka-cho, Obu, Aichi 474-8522, Japan.

出版信息

FEBS Lett. 2005 Mar 28;579(9):1995-2000. doi: 10.1016/j.febslet.2005.02.048.

DOI:10.1016/j.febslet.2005.02.048

PMID:15792809

Abstract

Alzheimer's disease is characterized by numerous amyloid-beta peptide (Abeta) plaques surrounded by microglia. Here we report that Abeta induces the proliferation of the mouse microglial cell line Ra2 by increasing the expression of macrophage colony-stimulating factor (M-CSF). We examined signal cascades for Abeta-induced M-CSF mRNA expression. The induction of M-CSF was blocked by a phosphatidylinositol 3 kinase (PI3-kinase) inhibitor (LY294002), a Src family tyrosine kinase inhibitor (PP1) and an Akt inhibitor. Electrophoretic mobility shift assays showed that Abeta enhanced NF-kappaB binding activity to the NF-kappaB site of the mouse M-CSF promoter, which was blocked by LY294002. These results indicate that Abeta induces M-CSF mRNA expression via the PI3-kinase/Akt/NF-kappaB pathway.

摘要

阿尔茨海默病的特征是存在众多被小胶质细胞包围的β淀粉样肽（Aβ）斑块。在此我们报告，Aβ通过增加巨噬细胞集落刺激因子（M-CSF）的表达来诱导小鼠小胶质细胞系Ra2的增殖。我们研究了Aβ诱导M-CSF mRNA表达的信号级联反应。M-CSF的诱导被磷脂酰肌醇3激酶（PI3激酶）抑制剂（LY294002）、Src家族酪氨酸激酶抑制剂（PP1）和Akt抑制剂所阻断。电泳迁移率变动分析表明，Aβ增强了NF-κB与小鼠M-CSF启动子的NF-κB位点的结合活性，而这被LY294002所阻断。这些结果表明，Aβ通过PI3激酶/Akt/NF-κB途径诱导M-CSF mRNA表达。