Protective Effects of L-3-n-Butylphthalide Against H2O2-Induced Injury in Neural Stem Cells by Activation of PI3K/Akt and Mash1 Pathway
Protective Effects of L-3-n-Butylphthalide Against H2O2-Induced Injury in Neural Stem Cells by Activation of PI3K/Akt and Mash1 Pathway
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L-3-正丁基苯酞通过激活 PI3K/Akt 和 Mash1 通路对 H2O2 诱导的神经干细胞损伤的保护作用
DOI：
10.1016/j.neuroscience.2018.10.003
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发表时间：
2018-11-21
期刊：
影响因子：
3.3
通讯作者：
Peng, Ying
中科院分区：
文献类型：
--
作者：
Wang, Shan;Huang, Longjian;Peng, Ying
据报道，氧化应激会对发育中的大脑造成损害。l -3-正丁基酞（L-NBP）在不同动物和细胞模型中均能抑制神经元细胞凋亡并具有神经发生作用。然而，L-NBP是否能够保护神经干细胞（NSCs）的神经发生过程免受氧化应激损伤尚不清楚。在本研究中，我们评估了L-NBP在NSCs中对h2o2诱导损伤的神经保护作用及其可能的机制。结果表明，L-NBP通过上调cyclin D1来促进NSCs的增殖，PI3K/Akt可能是这一过程中的靶点。随后，L-NBP被发现促进NSCs的迁移，N-cadherin可能参与其中。免疫荧光染色检测NSC分化，结果显示L-NBP能促进NSCs向神经元分化。由于短干扰RNA抑制内源性Mash1的表达可阻断l - nbp促进的神经元分化，因此，毛囊鳞片同源物1 （Mash1）表达的升高可能是关键因素。综上所述，L-NBP通过促进NSCs的增殖、迁移和神经分化，对h2o2诱导的NSCs损伤具有保护作用，提示L-NBP可能是一种潜在的基于神经发生的脑疾病治疗药物，如阿尔茨海默病（AD）。(c) 2018年。Elsevier Ltd.出版。版权所有。
It has been reported that oxidative stress could result in damage to the developing brain. L-3-n-butylphthalide (L-NBP) could inhibit neuronal cell apoptosis and has neurogenesis effect in different animal and cellular models. However, whether L-NBP could protect the process of neurogenesis in neural stem cells (NSCs) against oxidative stress injury is still unclear. Here, in the present study, we evaluated the neuroprotective effect of L-NBP in NSCs against H2O2-induced injury and the possible mechanisms. The results showed that L-NBP elevated the proliferation of NSCs by upregulating cyclin D1, and PI3K/Akt might be a possible target in this process. Subsequently, L-NBP was found to promote the migration of NSCs and N-cadherin might be involved in. NSC differentiation was measured using immunofluorescence staining and the results demonstrated that L-NBP could promote the NSCs to differentiate more into neurons. The elevation of achaete-scute homolog1 (Mash1) expression might be a key factor as attenuation of endogenous Mash1 expression by short-interfering RNA could block L-NBP-promoted neuronal differentiation. In summary, L-NBP exerts protective effects in NSCs against H2O2-induced injury by promoting the proliferation, migration and neural differentiation of NSCs, indicating that L-NBP might be a potential therapeutic agent for the neurogenesis-based treatment for some brain diseases, such as Alzheimer's disease (AD). (C) 2018 IBRO. Published by Elsevier Ltd. All rights reserved.