microRNA-15a和microRNA-195在电磁辐射致神经元线粒体功能障碍中的作用研究

项目名称： microRNA-15a和microRNA-195在电磁辐射致神经元线粒体功能障碍中的作用研究

项目编号： No.31200627

项目类型： 青年科学基金项目

立项/批准年度： 2013

项目学科： 生物物理、生化与生物分子学、生物力学与组织工程

项目作者： 卢永辉

作者单位： 中国人民解放军第三军医大学

项目金额： 23万元

中文摘要： 电磁辐射致中枢神经系统损伤的机制尚不清楚。我们前期研究表明，电磁辐射可引起神经元线粒体膜电位降低，ATP含量降低和氧化应激增强，并引起miR-15a和miR-195的表达上调。报道显示，miR-15a和miR-195的表达升高可引起线粒体功能障碍。据此我们推测，电磁辐射可能通过上调miR-15a和miR-195的表达，从而引起神经元线粒体功能障碍。本项目拟通过定性定量分析电磁辐射对神经细胞miR-15a/195表达及其在线粒体分布的影响，并通过上调和抑制miR-15a/195的表达，明确miR-15a/195在电磁辐射致皮层神经元线粒体功能障碍中的作用；从miR-15a/195对COX3/ND3基因表达及线粒体呼吸链复合物IV/V活性调控环节，揭示电磁辐射后miR-15a/195表达改变引起神经细胞线粒体功能障碍的分子机制。通过研究，从新的角度为电磁辐射致中枢神经损伤的防护提供依据。

中文关键词： 电磁辐射；microRNA；线粒体功能损伤；胶质细胞；炎症反应

英文摘要： The mechanism underlying electromagnetic field (EMF)induced impairments of centrol never system(CNS) is not very clear. Increased expressions of miR-15a and miR-195 were recently reported to impair the mitochondrial function.Our previous study has showed that ATP content and membrane potential were reduced by EMF exposure, whereas the ROS content was increased by EMF exposure in cortical neurons. And,after the EMF exposure, the expressions of miR-15a and miR-195 increased. Thus, we speculate that the EMF exposure may cause the mitochondrial dysfunction by increasing the expressions of miR-15a and miR-195. This study will evaluate the effects of EMF exposure on the miR-15a/195 expression and distribution in neurons. The role of miR-15a/195 in EMF-induced mitochondrial dysfunction will be investigated by up-regulating and suppressing expressions of miR-15a/195 in neurons. Considering the COX3 and ND3 gene contain the target sequences of miR-15a/195, the post-transcriptional suppression of miR-15a/195 on COX3 and ND3 gene expression is probably the mechanism by which miR-15a/195 impair mitochondrial function. To explore the mechanism underlyling EMF-induced neuronal mitochondrial dysfunction, this study will investigate the regulation of miR-15a/195 on translation of COX3 and ND3 gene mRNA. Then,the enzymatic activ

英文关键词： Electromagnetic field；microRNA；Mitochondrial dysfunction；glia；inflammation