Pramipexole Inhibits MPP+-Induced Neurotoxicity by miR-494-3p/BDNF
Pramipexole Inhibits MPP+-Induced Neurotoxicity by miR-494-3p/BDNF
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DOI：
10.1007/s11064-019-02910-5
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发表时间：
2020-02-01
影响因子：
4.4
通讯作者：
Dai, Li
中科院分区：
文献类型：
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作者：
Deng, Chao;Zhu, Jianping;Dai, Li
普拉克索(PPX)是治疗帕金森病的常用药物。然而，PPX在帕金森氏病进展中的作用机制在很大程度上仍不清楚。本研究旨在研究PPX在1-甲基-4-苯基吡啶(MPP+)诱导的神经母细胞瘤细胞中的作用，并探讨PPX与miR-494-3p/脑源性神经营养因子(BDNF)轴的相互作用。用MPP+攻击SK-N-SH和CHP 212细胞作为帕金森病细胞模型，与PPX共同孵育。用实时定量聚合酶链式反应或免疫印迹法检测miR-494-3p和BDNF的表达水平。通过细胞凋亡、炎症反应和氧化应激检测神经毒性。荧光素酶报告和RNA免疫沉淀实验证实miR-494-3p与BDNF之间存在靶向结合。经MPP+处理的SK-N-SH和CHP 212细胞MIR-494-3p表达增加，BDNF水平降低，而PPX的作用被逆转。普拉克索可减轻MPP+处理的SK-N-SH和CHP 212细胞的细胞凋亡、炎症反应和氧化应激。敲除miR-494-3p还可抑制MPP+对SK-N-SH和CHP 212细胞的神经毒性作用。BDNF被确认为miR-494-3p的靶标，其沉默减弱了miR-494-3p对MPP+诱导的神经毒性的抑制作用。此外，加入miR-494-3p和沉默BDNF可减轻PPX对MPP+诱导的神经毒性的影响。PPX通过降低miR-494-3p和增加BDNF，抑制MPP+诱导的SK-N-SH和CHP 212细胞的神经毒性，提示PPX对帕金森病有潜在的治疗作用。
Pramipexole (PPX) is a common drug for the treatment of Parkinson's disease. However, the mechanism allows PPX in the progression of Parkinson's disease remains largely unknown. This study aimed to investigate the role of PPX in 1-Methyl-4-phenylpyridinium (MPP+)-treated neuroblastoma cells and explore the interaction between PPX and miR-494-3p/brain derived neurotrophic factor (BDNF) axis. SK-N-SH and CHP 212 cells challenged by MPP+ were used as cellular model of Parkinson's disease and incubated with PPX. The expression levels of miR-494-3p and BDNF were measured by quantitative real-time polymerase chain reaction or western blot. Neurotoxicity was investigated by cell apoptosis, inflammatory response and oxidative stress. The target association between miR-494-3p and BDNF was confirmed by luciferase reporter and RNA immunoprecipitation assays. miR-494-3p expression was increased and BDNF level was decreased in MPP+-treated SK-N-SH and CHP 212 cells, which were reversed by introduction of PPX. Pramipexole attenuated cell apoptosis, inflammatory response and oxidative stress in MPP+-treated SK-N-SH and CHP 212 cells. Knockdown of miR-494-3p also suppressed neurotoxicity induced by MPP+ in SK-N-SH and CHP 212 cells. BDNF was validated as a target of miR-494-3p and its silence abated the suppressive effect of miR-494-3p on MPP+-induced neurotoxicity. Moreover, addition of miR-494-3p and silence of BDNF mitigated the effect of PPX on MPP+-induced neurotoxicity. PPX inhibited MPP+-induced neurotoxicity in SK-N-SH and CHP 212 cells by decreasing miR-494-3p and increasing BDNF, indicating the potential therapeutic effect of PPX on Parkinson's disease.