重离子辐射诱导斑马鱼精原细胞凋亡的线粒体磷酸化蛋白质组调控机制研究

项目名称： 重离子辐射诱导斑马鱼精原细胞凋亡的线粒体磷酸化蛋白质组调控机制研究

项目编号： No.11505244

项目类型： 青年科学基金项目

立项/批准年度： 2016

项目学科： 数理科学和化学

项目作者： 李鸿岩

作者单位： 中国科学院近代物理研究所

项目金额： 23万元

中文摘要： 重离子辐射诱导精原细胞凋亡会产生严重的突变效应，因此，重离子辐射诱导精原细胞凋亡调控机制的研究对空间和环境辐射损伤评估及防护均有实际参考价值。近年来，线粒体在细胞凋亡中的作用被进一步证实，而蛋白质的磷酸化和去磷酸化这一可逆过程直接参与细胞的信号转导和凋亡全过程。由于线粒体介导的细胞凋亡的信号传递系统至今未阐明清楚，因此，如何明确磷酸化蛋白在细胞凋亡过程起到的调控作用，是目前急需解决的问题。本项目以磷酸化蛋白质组学为手段，以建立线粒体磷酸化蛋白信号转导网络为切入点，以基于重离子辐射诱导斑马鱼精原细胞凋亡的线粒体磷酸化蛋白质组调控机制研究为主线，以发现重要的磷酸化调控蛋白为重点，对完善重离子辐射诱导精原细胞凋亡的机理研究提供新思路，为揭示精原细胞凋亡导致的疾病机制研究提供理论依据。此外，也为保护辐射环境工作者、放疗病人、宇航员和太空旅行者的健康安全保护提供科学依据。

中文关键词： 重离子辐射；斑马鱼；精原细胞凋亡；磷酸化蛋白质组；调控机制

英文摘要： Heavy ion radiation (HIR) has a significant apoptotic effect and can induce damaging mutations in spermatogonia. In order to define the mechanisms underlying induction of apoptosis by HIR in spermatogonia, reference values of spatial and environmental radiation damage assessment and radiation protection are needed. Mitochondria are explicitly involved in programmed cell apoptosis signal transduction pathways. Protein phosphorylation is a reversible process that directly regulates cell signal transduction and apoptosis. However, due to the complexity involved, the mitochondria-mediated apoptosis signaling system has not yet been fully elucidated. Clarifying the function of proteins involved in mitochondria-mediated apoptosis, and building a signal transduction network to define the regulatory role of protein phosphorylation in this process are key goals. Phosphoproteomics approaches may define mitochondrial protein phosphorylation signal transduction networks in zebrafish spermatogonia. These could then be used to elucidate the mechanisms underlying heavy ion-induced apoptosis in spermatogonia. This may in turn facilitate the discovery of important phosphorylated protein regulatory nodes. In addition, this study is of significance for our mechanistic understanding of the effects of HIR-induced damage in reproductive biology more generally. This knowledge could be used to protect individuals exposed to environmental radiation at work, patients undergoing radiotherapy, and astronauts and space travelers.

英文关键词： Heavy ion radiation;Zebrafish;Spermatogonia apoptosis ; Phosphoproteome;Regulatory mechanism