SH-SY5Y型
化学
一氧化氮
陶氏病
脱磷
τ蛋白
免疫印迹
生物物理学
发病机制
蛋白酶体
磷酸化
生物化学
细胞生物学
阿尔茨海默病
神经退行性变
生物
细胞培养
内科学
神经母细胞瘤
医学
疾病
免疫学
磷酸酶
遗传学
有机化学
基因
作者
Muneaki Takahashi,Yo Chin,Takashi Nonaka,Masato Hasegawa,Nobuo Watanabe,Takao Arai
标识
DOI:10.1016/j.neulet.2011.12.067
摘要
Presence of cytoplasmic tau aggregates is a hallmark of brains in patients with tauopathies such as Alzheimer's disease. However, the mechanism underlying formation of these insoluble tau aggregates remains elusive. In this study, we investigated the impact of prolonged nitric oxide (NO) exposure on neuronal SH-SY5Y cells overexpressing human tau. Treatment with the NO donor DETA NONOate for up to 48h resulted in an increase in S-nitrosation of cellular proteins, inactivation of proteasome, and impairment of respiration. Western blot analysis of Triton X-soluble fractions of NO-treated cells revealed that persistent NO treatment increased heterogeneity in tau molecule size, as a result of dephosphorylation, and induced the formation of sodium dodecyl sulfate (SDS)-stable oligomeric tau aggregates, stabilized by disulfide bonds. Moreover, further NO treatment induced the formation of SDS-stable insoluble tau mega-aggregates that were composed of dephosphorylated full-length tau molecules and other proteins, and were stabilized through disulfide bonds. Evaluation of the role of these tau aggregates as potential seeds for tau fibrillization and elucidation of their formation mechanism in our model, could lead to better understanding of the pathogenesis of tauopathies.
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