Beta-amyloid-induced neurotoxicity of a hybrid septal cell line associated with increased tau phosphorylation and expression of beta-amyloid precursor protein.
Beta-amyloid-induced neurotoxicity of a hybrid septal cell line associated with increased tau phosphorylation and expression of beta-amyloid precursor protein.
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β-淀粉样蛋白诱导的混合间隔细胞系神经毒性与 tau 磷酸化和 β-淀粉样前体蛋白表达增加相关。
DOI：
10.1046/j.1471-4159.1997.69030978.x
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发表时间：
1997
影响因子：
4.7
通讯作者：
Appel,SH
中科院分区：
文献类型：
--
作者：
Le,WD;Xie,WJ;Kong,R;Appel,SH
最近的证据表明，β‐淀粉样蛋白肽（β‐AP）可能诱导tau蛋白磷酸化，导致微管结合能力的丧失和成对螺旋细丝的形成。然而，β - AP增加tau磷酸化的机制尚不清楚。利用杂交鼻中隔细胞系SN56，我们证明了聚集的β‐ap1 - 40处理导致细胞损伤。AT8、PHF‐1、tau‐1和tau‐5抗体的免疫化学检测显示，随着细胞损伤，磷酸化tau蛋白和总tau蛋白水平升高。碱性磷酸酶处理消除了AT8和PHF‐1的免疫反应性，证实tau磷酸化位点至少在ser199 /202和Ser396。随着tau磷酸化的增加，细胞相关和分泌的β -淀粉样蛋白前体蛋白（β - APP）的免疫反应性显著升高。β - APP反义寡核苷酸的应用降低了β - APP的表达和磷酸化tau蛋白的免疫反应性。控制肽β‐ap1 - 28对tau磷酸化没有显著影响，尽管它略微增加了细胞相关的β‐APP。这些结果表明，β ap1 - 40诱导的tau磷酸化可能与变性神经元中β - APP表达增加有关。
Recent evidence suggests that β‐amyloid peptide (β‐AP) may induce tau protein phosphorylation, resulting in loss of microtubule binding capacity and formation of paired helical filaments. The mechanism by which β‐AP increases tau phosphorylation, however, is unclear. Using a hybrid septal cell line, SN56, we demonstrate that aggregated β‐AP1–40treatment caused cell injury. Accompanying the cell injury, the levels of phosphorylated tau as well as total tau were enhanced as detected immunochemically by AT8, PHF‐1, Tau‐1, and Tau‐5 antibodies. Alkaline phosphatase treatment abolished AT8 and PHF‐1 immunoreactivity, confirming that the tau phosphorylation sites were at least at Ser199/202and Ser396. In association with the increase in tau phosphorylation, the immunoreactivity of cell‐associated and secreted β‐amyloid precursor protein (β‐APP) was markedly elevated. Application of antisense oligonucleotide to β‐APP reduced expression of β‐APP and immunoreactivity of phosphorylated tau. Control peptide β‐AP1–28did not produce significant effects on tau phosphorylation, although it slightly increased cell‐associated β‐APP. These results suggest that βAP1–40‐induced tau phosphorylation may be associated with increased β‐APP expression in degenerated neurons.