中国药理学通报2017，Vol.33Issue(6)：761-767,7.DOI:10.3969/j.issn.1001-1978.2017.06.006
自噬降低异常磷酸化tau蛋白所致的神经细胞毒性
Autophagy alleviates neuronal toxicityinduced by abnormally phosphorylated tau protein
摘要
Abstract
Aim To observe the effects of rapamycin (Rapa) and starvation-induced autophagy on the morphology of neuronal cells, tau protein aggregation and expression of phosphorylated tau protein, to explore the possible mechanism of cytoprotective effect of these two classical autophagy inducers on phosphorylated tau expressing cells.Methods N2a cells were transfected with GFP-tau plasmid, and equal amount of empty vector was used as control.Then cells were incubated with or without okadaic acid(OA) for 12 h, followed by treatment with autophagy inducers rapamycin(Rapa) and EBSS, autophagy inhibitor Bafilomycin A1(Baf A1) for 6 h.DAB was used to observe tau expression and cell morphology.Confocal microscopy was used to observe the intracellular tau aggregation.TUNEL assay and cleaved caspase-3 level were used to detect cell apoptosis.Immunoblot was used to detect the expression of phosphorylated tau and autophagy-related proteins.Results Our study showed that the N2a cells treated with OA exhibited small cell body, retracted processes and increased tau aggregation, compared with only tau-expressing cells.Rapa and EBSS treatment significantly improved cell morphology, decreased tau aggregation and reduced cell apoptosis.On the contrary, Baf A1 treatment induced aberrant cell shape and increased tau aggregation and cell apoptosis.In addition, Rapa significantly decreased the high molecular weight, phosphorylated tau whereas EBSS especially decreased the low molecular weight phosphorylated tau.Conclusions Rapa and EBSS is alleviate hyperphosphorylated tau-induced cytotoxicity through different mechanism.Rapamycin mainly decreases phosphorylated tau oligomers, while EBSS liable to decrease the soluble phosphorylated tau.关键词
tau/磷酸化/雷帕霉素/自噬/蛋白降解/细胞毒性Key words
tau/phosphorylation/rapamycin/autophagy/protein degradation/cytotoxicity分类
医药卫生引用本文复制引用
丁倩,张瑾,马钰泱,沈玉君,沈玉先,冯利杰..自噬降低异常磷酸化tau蛋白所致的神经细胞毒性[J].中国药理学通报,2017,33(6):761-767,7.基金项目
国家自然科学基金资助项目(No 81302755) （No 81302755）
