Xu Shunjiang, Zhang Rui, Niu Jingya, Cui Dongsheng, Xie Bing, Zhang Binggui, Lu Kang, Yu Wenjun, Wang Xueyi, Zhang Qingfu
Central Laboratory, The First Hospital of Hebei Medical University, Shijiazhuang 050031, China.
Int J Mol Sci. 2012 Dec 11;13(12):16945-60. doi: 10.3390/ijms131216945.
Oxidative stress plays a critical role in the etiology and pathogenesis of neurodegenerative disorders, and the molecular mechanisms that control the neuron response to ROS have been extensively studied. However, the oxidative stress-effect on miRNA expression in hippocampal neurons has not been investigated, and little is known on the effect of ROS-modulated miRNAs on cell function. In this study, H(2)O(2) was used to stimulate the mouse primary hippocampal neurons to develop an oxidative stress cell model. The alterations of miRNAs expression were detected by microarray analysis and five miRNAs were validated by real-time RT-PCR. The bioinformatic analysis of deregulated miRNAs was performed to determine their potential roles in the pathogenesis of neurological disorders. We found that H(2)O(2) mediated a total of 101 deregulated miRNAs, which mainly took part in the regulation of the MAPK pathway. Among them, miR-135b and miR-708 were up-regulated significantly and their targets were predicted to be involved in DNA recombination, protein ubiquitination, protein autophosphorylation and development of neurons. These results demonstrated that oxidative stress alters the miRNA expression profile of hippocampal neurons, and the deregulated miRNAs might play a potential role in the pathogenesis of neurodegenerative diseases, such as Alzheimer's disease (AD).
氧化应激在神经退行性疾病的病因学和发病机制中起着关键作用，并且控制神经元对活性氧（ROS）反应的分子机制已得到广泛研究。然而，氧化应激对海马神经元中微小RNA（miRNA）表达的影响尚未得到研究，关于ROS调节的miRNA对细胞功能的影响也知之甚少。在本研究中，使用过氧化氢（H₂O₂）刺激小鼠原代海马神经元以建立氧化应激细胞模型。通过微阵列分析检测miRNA表达的变化，并通过实时逆转录聚合酶链反应（RT-PCR）验证了5种miRNA。对失调的miRNA进行生物信息学分析，以确定它们在神经疾病发病机制中的潜在作用。我们发现H₂O₂介导了总共101种失调的miRNA，它们主要参与丝裂原活化蛋白激酶（MAPK）途径的调节。其中，miR-135b和miR-708显著上调，预测它们的靶标参与DNA重组、蛋白质泛素化、蛋白质自磷酸化和神经元发育。这些结果表明，氧化应激改变了海马神经元的miRNA表达谱，失调的miRNA可能在神经退行性疾病如阿尔茨海默病（AD）的发病机制中发挥潜在作用。
