Li Fang, Chen Anbao, Zhang Jie
Department of Emergencyinternal Medicine, The Second Affiliated Hospital of Kunming Medical University Kunming 650221, China.
Department of Hepatology, The First Affiliated Hospital of Kunming Medical University Kunming 650032, China.
Am J Transl Res. 2019 Mar 15;11(3):1780-1788. eCollection 2019.
The protective effect of zoanthamine on Alzheimer's disease by enhancing differentiation of neural stem cells (NSCs) was evaluated. NSCs were isolated from C57BL/6 mice and assessed by cell viability and apoptosis assays. The cells were separated into five different groups: green fluorescent protein (GFP; transfected with GFP), amyloid precursor protein (APP; transfected with APP), APP + zoanthamine, APP + miR-9 inhibitor, and APP + miR-9 inhibitor + zoanthamine. The effects of zoanthamine on the differentiation of NSCs was determined. Moreover, the effects of zoanthamine on the expression of miR-9 and Notch signalling pathway members was assessed by western blot analysis and reverse-transcription polymerase chain reaction. There was a significant increase in cell viability and a decrease in apoptosis of NSCs in the APP + zoanthamine group compared with the APP group. Treatment with zoanthamine attenuated miR-9 expression and neuronal cell differentiation in APP-treated NSCs. Moreover, in the APP + miR-9 inhibitor group, neuronal cell differentiation and miR-9 expression were significantly reduced, and treatment with zoanthamine reduced the number of differentiated cells and miR-9 expression compared with the APP + miR-9 inhibitor group. There was a significant reduction in the expression of Hes1 and NICD proteins in the APP + zoanthamine group relative to the APP group. In addition, the levels of Hes1 and NICD were enhanced by inhibition of miR-9 but zoanthamine prevented these increases. In conclusion, these results suggest that treatment with zoanthamine enhances the differentiation of NSCs by regulating Notch signalling via elevated miR-9 expression.
评估了海葵胺通过增强神经干细胞（NSCs）分化对阿尔茨海默病的保护作用。从C57BL/6小鼠中分离出神经干细胞，并通过细胞活力和凋亡检测进行评估。将细胞分为五个不同的组：绿色荧光蛋白（GFP；转染GFP）、淀粉样前体蛋白（APP；转染APP）、APP + 海葵胺、APP + miR-9抑制剂以及APP + miR-9抑制剂 + 海葵胺。测定了海葵胺对神经干细胞分化的影响。此外，通过蛋白质免疫印迹分析和逆转录聚合酶链反应评估了海葵胺对miR-9表达和Notch信号通路成员的影响。与APP组相比，APP + 海葵胺组神经干细胞的细胞活力显著增加，凋亡减少。海葵胺处理减弱了APP处理的神经干细胞中miR-9的表达和神经元细胞分化。此外，在APP + miR-9抑制剂组中，神经元细胞分化和miR-9表达显著降低，与APP + miR-9抑制剂组相比，海葵胺处理减少了分化细胞数量和miR-9表达。相对于APP组，APP + 海葵胺组中Hes1和NICD蛋白的表达显著降低。此外，抑制miR-9可增强Hes1和NICD的水平，但海葵胺可阻止这些增加。总之，这些结果表明，海葵胺处理通过升高miR-9表达调节Notch信号通路，从而增强神经干细胞的分化。
