Tau蛋白过度磷酸化诱导Aβ生成抑制THP-1细胞ABCA1的表达  

Hyperphosphorylation of tau protein increased the β-amyloid protein production and down-expressed ATP-binding cassette transporter A1 expression

作　　者：邸云峰[1] 韦丽华[1] 焦玉蓉[1] 王树人[1] 

机构地区：[1]四川大学华西基础与法医学院病理生理教研室,四川成都610041

出　　处：《四川生理科学杂志》2010年第2期63-66,共4页Sichuan Journal of Physiological Sciences

摘　　要：目的:探讨过度磷酸化Tau蛋白在动脉粥样硬化发生中的作用及其可能机制。方法:体外培养人单核细胞系THP-1,经佛波酯诱导分化为巨噬细胞,建立人盐洗血小板与THP-1(人单核细胞)源性巨噬细胞共孵育生成泡沫细胞的体外模型。免疫细胞化学法检测过磷酸化Tau蛋白和β淀粉样蛋白的生成。用岗田酸(OA)诱导其Tau蛋白过磷酸化,Western blot观察Tau蛋白T231和S396两个位点磷酸化程度及β淀粉样蛋白水平,RT-PCR法检测三磷酸腺苷结合盒转运体A1(ABCA1)mRNA表达水平。结果:OA引起Tau蛋白剂量依赖的过度磷酸化,并增加β淀粉样蛋白的生成,同时下调ABCA1 mRNA水平的表达(P<0.05)。结论:Tau蛋白过度磷酸化诱导β淀粉样蛋白的生成并下调ABCA1 mRNA水平的表达,可能是动脉粥样硬化斑块形成和发展的机制之一。Objective： To investigate the potential role and the mechanism of hyperphosphorylated Tau protein in the pathogenesis of atherosclerosia. Methods： Human monocyte cell THP-1 cells was cultured and induced to macrophage by PMA treatment, and the hyperphosphorylated tau protein and β-amyloid protein were examined by immunocytochemical method. Washed human platelets and the macrophages were co-incubated to induce the foam cell formation, and then stimulated by Okadaic acid（OA）, the hyperphosphorylated level of Tau protein and β-amyloid protein was examined by Western blot,ABCA1 mRNA expression was detected by RT- PCR. Result： OA induced the hyperphosphorylation of Tau protein in a dose-dependent manner, and a parallel increase of β-Amyloid protein, while the ABCA1 mRNA level was down-expressed in an inverted patter. Coclusions： Hyperphosphorylation of Tau protein induced the production of β-amyloid protein and down-regulated the ABCA1 expression, which may be involved in the pathogenesis of atherosclerosis.

关 键 词：动脉粥样硬化 阿尔茨海默尔病 TAU蛋白 淀粉样蛋白β ATP结合盒转运体A1 岗田酸 

分 类 号：R749.16[医药卫生—神经病学与精神病学]