Up-regulation of microRNA-375 ameliorates the damage of dopaminergic neurons, reduces oxidative stress and inflammation in Parkinson's disease by inhibiting SP1
Up-regulation of microRNA-375 ameliorates the damage of dopaminergic neurons, reduces oxidative stress and inflammation in Parkinson's disease by inhibiting SP1
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microRNA-375 的上调可改善多巴胺能神经元的损伤，通过抑制 SP1 减少帕金森病的氧化应激和炎症
DOI：
10.18632/aging.102649
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发表时间：
2020-01-15
期刊：
影响因子：
5.2
通讯作者：
Tian, Jin-Yong
中科院分区：
文献类型：
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作者：
Cai, Li-Jun;Tu, Li;Tian, Jin-Yong
背景：本研究旨在通过下调转录因子特异性蛋白1（SP1）来探讨微小RNA - 375（miR - 375）升高在帕金森病多巴胺能神经元中的保护作用。
结果：成功构建的帕金森病大鼠模型表现出神经行为改变聚集、神经炎症反应和氧化应激增加以及多巴胺含量降低。用过表达的miR - 375处理的帕金森病大鼠通过下调SP1，显示出神经行为改变改善、神经炎症反应和氧化应激减轻、多巴胺含量升高以及神经元凋亡减少。SP1的上调逆转了miR - 375上调对帕金森病的保护作用。
结论：miR - 375的上调通过抑制SP1改善了帕金森病中多巴胺能神经元的损伤，减少了氧化应激和炎症。
方法：通过定向注射6 - 羟基多巴胺损伤黑质纹状体建立帕金森病大鼠模型。对成功构建模型的帕金森病大鼠进行脑室内注射miR - 375模拟物或pcDNA3.1 - SP1。评估miR - 375和SP1在帕金森病大鼠神经行为改变、神经炎症反应、氧化应激、多巴胺含量以及黑质中凋亡相关蛋白表达方面的作用。通过生物信息学分析和双荧光素酶报告基因检测确定miR - 375和SP1的靶向关系。
Background: This study is conducted to investigate the protective role of elevated microRNA-375 (miR-375) in dopaminergic neurons in Parkinson's disease through down-regulating transcription factor specificity protein 1 (SP1).Results: The successfully modeled rats with Parkinson's disease showed aggregated neurobehavioral change, increased neuroinflammatory response and oxidative stress, and lowered dopamine content. Parkinson's disease rats treated with overexpressed miR-375 displayed improved neurobehavioral change, ameliorated neuroinflammatory response and oxidative stress, heightened dopamine content and abated neuronal apoptosis by down-regulating SP1. Up-regulation of SP1 reversed the protective effect of upregulated miR-375 on Parkinson's disease.Conclusion: Up-regulation of miR-375 ameliorated the damage of dopaminergic neurons, reduced oxidative stress and inflammation in Parkinson's disease by inhibiting SP1.Methods: Parkinson's disease rat model was established by targeted injection of 6-hydroxydopamine to damage the substantia nigra striatum. The successfully modeled Parkinson's disease rats were intracerebroventricularly injected with miR-375 mimics or pcDNA3.1-SP1. The functions of miR-375 and SP1 in neurobehavioral change, neuroinflammatory response, oxidative stress, dopamine content and expression of apoptosis-related proteins in the substantia nigra of Parkinson's disease rats were evaluated. The target relation of miR-375 and SP1 was confirmed by bioinformatics analysis and dual luciferase reporter gene assay.