The Fourth Ward, Department of Neurology, The Third Affiliated Hospital of Qiqihar Medical University, Qiqihar 161000, PR China.
Director's Office, The Third Affiliated Hospital of Qiqihar Medical University, Qiqihar 161000, PR China.
Brain Res. 2019 Nov 1;1722:146331. doi: 10.1016/j.brainres.2019.146331. Epub 2019 Jul 10.
Recently, it has been demonstrated that microRNA-137 (miR-137) plays a vital role in the induction of oxidative stress of neurons in Parkinson's disease (PD). Herein, the study aimed to investigate the effects of serum exosomal miR-137 on oxidative stress injury of neurons in PD. Microarray analysis was adopted to screen the PD-related differential expressed genes and predict the interaction between OXR1 and miR-137 in PD. It was found that OXR1 was down-regulated while miR-137 was up-regulated in PD. Additionally, miR-137 targeted OXR1 and negatively regulated its expression. Mouse and neuron models of PD were established to mimic the pathological changes, especially oxidative stress injury induced by PD. The significance of miR-137 and OXR1 in oxidative stress injury was investigated in neuron model of PD using gain- and loss-of-function approaches. The obtained data exhibited that inhibition of miR-137 or up-regulation of OXR1 ameliorated PD-induced oxidative stress injury, reduced pole-climbing time, but increased score for traction test as well as promoted viability and decreased apoptosis of neurons in PD model, accompanied with decreased MDA content and ROS levels, and increased SOD levels. Furthermore, PD mice were injected with serum-derived exosomes or neurons in PD models were exposed to exosomes derived from serum of PD mice. Loss-of-function experiments using miR-137 antagomir exhibited that inhibition of exosomal miR-137 ameliorated PD-induced oxidative stress injury in vitro, reduced pole-climbing time but increased score for traction test in vivo. Collectively, down-regulation of exosomal miR-137 alleviates oxidative stress injury in PD by up-regulating OXR1.
最近，研究表明 microRNA-137（miR-137）在帕金森病（PD）神经元氧化应激诱导中发挥着重要作用。本研究旨在探讨血清外泌体 miR-137 对 PD 神经元氧化应激损伤的影响。采用微阵列分析筛选与 PD 相关的差异表达基因，并预测 PD 中 OXR1 和 miR-137 之间的相互作用。结果发现，PD 中 OXR1 下调而 miR-137 上调。此外，miR-137 靶向 OXR1 并负调控其表达。建立了 PD 小鼠和神经元模型以模拟病理变化，特别是 PD 诱导的氧化应激损伤。通过 gain-和 loss-of-function 方法在 PD 神经元模型中研究了 miR-137 和 OXR1 在氧化应激损伤中的意义。获得的数据表明，抑制 miR-137 或上调 OXR1 可改善 PD 诱导的氧化应激损伤，减少爬杆时间，但增加牵引试验评分，促进 PD 模型中神经元的活力，减少凋亡，同时降低 MDA 含量和 ROS 水平，增加 SOD 水平。此外，向 PD 小鼠注射血清衍生的外泌体或使 PD 模型中的神经元暴露于来自 PD 小鼠血清的外泌体。使用 miR-137 拮抗剂进行的 loss-of-function 实验表明，抑制外泌体 miR-137 可改善体外 PD 诱导的氧化应激损伤，减少爬杆时间，但增加体内牵引试验评分。总之，下调外泌体 miR-137 通过上调 OXR1 减轻 PD 中的氧化应激损伤。
