运动促衰老卫星细胞成肌分化中线粒体嵴成熟及活性氧调控机制研究

项目名称： 运动促衰老卫星细胞成肌分化中线粒体嵴成熟及活性氧调控机制研究

项目编号： No.31200894

项目类型： 青年科学基金项目

立项/批准年度： 2013

项目学科： 生理学与整合生物学

项目作者： 薄海

作者单位： 中国人民武装警察部队后勤学院

项目金额： 23万元

中文摘要： 卫星细胞成肌分化能力降低是衰老性肌萎缩发生机制之一。适量运动训练可降低衰老卫星细胞内氧化应激水平，提高成肌分化能力，但具体机制尚不清楚。研究表明，成肌分化是包括嵴成熟在内的线粒体重构过程。我们前期工作证明，活性氧（ROS）过高产生氧化应激损伤线粒体稳态，运动训练可促进线粒体重构以实现健康效应，其中一定水平ROS是必要信号分子。本研究从ROS生理/病理双重作用角度探讨运动促衰老卫星细胞成肌分化的机制：1）原代培养衰老及运动干预小鼠卫星细胞并体外诱导分化，动态观察成肌分化的启动和进程中，ROS水平、线粒体嵴成熟及相关信号通路的变化规律；2）应用RNAi技术，阐明Mitofilin介导的线粒体嵴成熟对C2C12成肌细胞分化的影响及机制；3）外源性不同水平H2O2及mTOR激动剂和抑制剂干预C2C12成肌细胞，探讨不同水平ROS对线粒体嵴成熟的调控机制，及mTORC1在其中的作用。

中文关键词： 衰老；运动；成肌分化；线粒体嵴成熟；活性氧

英文摘要： Satellite cells myogenic differentiation has been shown to play a key role in sacopenia. It has been shown that moderate-intensity exercise training reduces oxidative stress in aged satellite cells. Analysis of mitochondria suggests a numerical increase of mitochondrial cristae from the undifferentiated to differentiated condition during myogenic differentiation, suggesting that mitochondrial crisae maturation may have a role in myogenesis. In previous works, we have shown that redox signaling involved in exercise induced mitochondrial dynamic remodeling. In this project, we will study the role of reactive oxygen specise (ROS) in regulation of exercise on myogenic differentiation in aged satellite cells. 1) Satellite cells were prepaired from aged rats and exercise training rats. To investigate the relationship among ROS, mitochondrial crisae maturation, myogenesis performation, and relative signaling molecule during myogenic differentiation. 2) To observe the effect of Mitofiline on mitochondrial crisae maturation, ATP production, and myogenesis performation during myogenic differentiation. 3) To examine the potential mechanisms involed in different dose of H2O2 regulation of mTORC1 signaling and mitochondrial dynamic remodeling during myogenic differentiation.

英文关键词： Aged；Exercise；Myogenic differentiation；Mitochondrial crisae maturation；Reactive oxygen species