Li Yanmin, Pang Jianmin, Wang Jing, Dai Guining, Bo Qianlan, Wang Xiayue, Wang Wei
Department of Neurology, The First Hospital of Hebei Medical University, Shijiangzhuang, Hebei 050031, China; Department of Neurology, Hebei Hospital of Xuanwu Hospital Capital Medical University, Shijiazhuang, Hebei, 050031, China.
Department of Neurology, The First Hospital of Hebei Medical University, Shijiangzhuang, Hebei 050031, China.
J Chem Neuroanat. 2023 Apr;129:102239. doi: 10.1016/j.jchemneu.2023.102239. Epub 2023 Feb 1.
Parkinson's disease (PD) is a complex neurodegenerative disorder and hampers normal living. It has been reported that programmed cell death 4 (PDCD4) is associated with tumor suppression, inflammatory response, and apoptosis.
The aim of this study was to investigate the role of PDCD4 in PD.
The in vivo and in vitro PD models were established by MPTP-induced mice and MMP+ stimulated MN9D cells, respectively. The expression of PDCD4 was detected by western blot. The MN9D cell viability and apoptosis were determined by MTT and flow cytometry assay. Moreover, the MN9D cell mitochondrial injury was evaluated by JC-1 staining.
In this study, PDCD4 was highly expressed in brain tissue of MPTP-induced PD mouse model. In a loss-function experiments, knockdown of PDCD4 promoted MN9D cell viability and allayed MPP+-triggered MN9D cell apoptosis. Furthermore, knockdown of PDCD4 ameliorated MPP+-evoked MN9D cell mitochondrial injury. Mechanically, knockdown of PDCD4 abolished the effect of MMP+ stimulation via activating phosphoinositide 3-kinase(PI3K)/AKT/mammalian target of rapamycin (mTOR) signal. Notably, the protective effects of shPDCD4 on cell apoptosis and mitochondrial injury were suppressed by PI3K inhibitor LY294002.
In summary,knockdown of PDCD4 ameliorates neural cell apoptosis and mitochondrial injury through activating the PI3K/AKT/mTOR signal, providing a novel target for PD treatment.
All data generated or analyzed during this study are included in this published article.
帕金森病（PD）是一种复杂的神经退行性疾病，会影响正常生活。据报道，程序性细胞死亡4（PDCD4）与肿瘤抑制、炎症反应和细胞凋亡有关。
本研究旨在探讨PDCD4在帕金森病中的作用。
分别通过MPTP诱导的小鼠和MMP +刺激的MN9D细胞建立体内和体外帕金森病模型。通过蛋白质免疫印迹法检测PDCD4的表达。采用MTT法和流式细胞术检测MN9D细胞活力和细胞凋亡情况。此外，通过JC-1染色评估MN9D细胞的线粒体损伤。
在本研究中，PDCD4在MPTP诱导的帕金森病小鼠模型的脑组织中高表达。在功能缺失实验中，敲低PDCD4可提高MN9D细胞活力，并减轻MPP +诱导的MN9D细胞凋亡。此外，敲低PDCD4可改善MPP +引起的MN9D细胞线粒体损伤。机制上，敲低PDCD4通过激活磷脂酰肌醇3激酶（PI3K）/蛋白激酶B（AKT）/雷帕霉素靶蛋白（mTOR）信号通路消除了MMP +刺激的作用。值得注意的是，PI3K抑制剂LY294002抑制了shPDCD4对细胞凋亡和线粒体损伤的保护作用。
综上所述，敲低PDCD4通过激活PI3K/AKT/mTOR信号通路改善神经细胞凋亡和线粒体损伤，为帕金森病的治疗提供了新的靶点。
本研究期间生成或分析的所有数据均包含在已发表的文章中。
