β‐Amyloid‐Induced Neurotoxicity of a Hybrid Septal Cell Line Associated with Increased Tau Phosphorylation and Expression of β‐Amyloid Precursor Protein
β‐Amyloid‐Induced Neurotoxicity of a Hybrid Septal Cell Line Associated with Increased Tau Phosphorylation and Expression of β‐Amyloid Precursor Protein
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与 Tau 磷酸化和 β-淀粉样前体蛋白表达增加相关的混合间隔细胞系的 β-淀粉样蛋白诱导的神经毒性
DOI：
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发表时间：
1997
期刊：
影响因子：
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通讯作者：
S. Appel
中科院分区：
文献类型：
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作者：
W. Le;W. Xie;R. Kong;S. Appel
摘要：最近的证据表明，β-淀粉样肽（β-AP）可能诱导 tau 蛋白磷酸化，导致微管结合能力丧失并形成配对螺旋丝。然而，β-AP 增加 tau 磷酸化的机制尚不清楚。使用杂交隔膜细胞系 SN56，我们证明聚集的 β-AP1-40 治疗会导致细胞损伤。通过 AT8、PHF-1、Tau-1 和 Tau-5 抗体进行免疫化学检测，随着细胞损伤，磷酸化 tau 蛋白和总 tau 蛋白的水平有所增强。碱性磷酸酶处理消除了 AT8 和 PHF-1 免疫反应性，证实 tau 磷酸化位点至少位于 Ser199/202 和 Ser396。随着 tau 磷酸化的增加，细胞相关和分泌的 β-淀粉样前体蛋白 (β-APP) 的免疫反应性显着升高。将反义寡核苷酸应用于 β-APP 会降低 β-APP 的表达和磷酸化 tau 的免疫反应性。对照肽 β-AP1-28 并未对 tau 磷酸化产生显着影响，尽管它略微增加了细胞相关的 β-APP。这些结果表明，βAP1-40 诱导的 tau 磷酸化可能与退化神经元中 β-APP 表达增加有关。
Abstract: 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‐AP1–40 treatment 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 Ser199/202 and 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‐AP1–28 did 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.
DOI：
10.1073/pnas.91.15.7104
发表时间：
1994-07-19
影响因子：
11.1
作者：
GREENBERG, SM;KOO, EH;KOSIK, KS
通讯作者：
KOSIK, KS
作为基底前脑模型的体外细胞培养物。
影响因子：
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作者：
Wainer,BH;Lee,HJ;Roback,JD;Hammond,DN
通讯作者：
Hammond,DN