Homer1a protects against neuronal injury via PI3K/AKT/mTOR signaling pathway
Homer1a protects against neuronal injury via PI3K/AKT/mTOR signaling pathway
复制标题
Homer1a 通过 PI3K/AKT/mTOR 信号通路防止神经元损伤
DOI：
10.1080/00207454.2019.1702535
复制
发表时间：
2020-02-01
影响因子：
2.2
通讯作者：
Duan, Faliang
中科院分区：
文献类型：
--
作者：
Wang, Yuan;Zhao, MingMing;Duan, Faliang
摘要目的：Homer 1a是突触后密度蛋白家族的成员，在神经元突触活动中起重要作用，并广泛参与神经系统疾病。本研究的目的是使用体外创伤性神经元损伤模型研究Homer 1a在调节神经元存活中的作用。材料与方法：分离大鼠神经元并鉴定。然后，用Homerla过表达或干扰载体处理细胞。Western blot检测Homerla、凋亡相关蛋白（caspase 3、caspase 8、caspase 9、Fas 1、Bax和p53）、自噬相关蛋白（LC 311和Beclin 1）的表达以及PI 3 K/AKT/mTOM通路的激活。另外，测定细胞存活率和凋亡率。结果如下：转染过表达载体和干扰载体后，Homer 1a的mRNA和蛋白表达分别显著增加和降低。Homer 1a的上调显著减轻了创伤性神经元损伤后的细胞凋亡，增强了细胞活力和自噬。Homer 1a过表达还显著降低了促凋亡蛋白caspase 3、caspase 8、caspase 9、FasL、Bax和p53在神经元中的表达。此外，创伤性神经元损伤后，神经元自噬增加，表现为Homer 1a过表达诱导的自噬体的更大积累和LC 3 II和Beclin 1的更高表达。此外，Homer 1a过表达抑制了PI 3 K/AKT/mTOR信号通路的激活。结论：这些结果表明Homer 1a可能通过caspase和PI 3 K/AKT/mTOR信号通路调节细胞凋亡和自噬来保护神经元免受创伤性损伤，可能是创伤性脑损伤的有效干预靶点。
Abstract Purpose: Homer1a is a member of the post-synaptic density protein family that plays an important role in neuronal synaptic activity and is extensively involved in neurological disorders. The aim of this study is to investigate the role of Homer1a in modulating neuronal survival using an in vitro traumatic neuronal injury model. Materials and methods: Neurons were extracted from rats and identifited. Then, the cells were treated with Homerla overexpression or interference vectors. Western blot was performed to evaluate the expression of Homerla, apoptosis-related proteins(caspase3, caspase8, caspase9, Fasl, Bax, and p53), autophagy-related proteins (LC3ll and Beclin1), and the activiation of PI3K/AKT/mTOM pathway. In addition, the cell viability and apoptosis rate were measured. Results: After transfection with overexpression or interference vectors, the mRNA and protein expression of Homer1a increased or decreased significantly, respectively. Upregulation of Homer1a significantly alleviated apoptosis and enhanced cell viability and autophagy after traumatic neuronal injury. Homer1a overexpression also significantly decreased the expression of the pro-apoptosis proteins caspase 3, caspase 8, caspase 9, Fasl, Bax, and p53 in neurons. Furthermore, neuron autophagy was increased after traumatic neuronal injury as demonstrated by the greater accumulation of autophagosomes and higher expression of LC3II and Beclin1 induced by Homer1a overexpression. In addition, Homer1a overexpression inhibited the activation of PI3K/AKT/mTOR signaling. Conclusion: These findings indicated that Homer1a potentially protects neurons from traumatic injury by regulating apoptosis and autophagy via the caspase and PI3K/AKT/mTOR signaling pathways and may be an effective intervention target in traumatic brain injury.