PARP-1/AIF信号通路在重离子诱导神经细胞凋亡中的调控作用研究

项目名称： PARP-1/AIF信号通路在重离子诱导神经细胞凋亡中的调控作用研究

项目编号： No.11205214

项目类型： 青年科学基金项目

立项/批准年度： 2013

项目学科： 物理学II

项目作者： 张录卫

作者单位： 中国科学院近代物理研究所

项目金额： 30万元

中文摘要： PARP-1是真核细胞中高度保守的核蛋白酶，PARP-1基因的突变、缺失及过表达都将直接影响到细胞凋亡进程。凋亡诱导因子（AIF）受过度活化PARP-1刺激，从线粒体转位至细胞核内触发非Caspases（胱天蛋白酶）依赖的细胞凋亡。业已证实，PARP-1/AIF通路在缺血再灌注引起的神经细胞凋亡中发挥决定性作用，但在重离子诱导的神经细胞凋亡中，PARP-1/AIF通路的作用地位以及两因子间的相互调控关系仍不明确。本项目拟采用重离子致神经细胞凋亡模型，利用激光扫描共聚焦显微镜技术、免疫共沉淀及慢病毒载体基因敲除或过表达,明确PARP-1与AIF的相互作用关系；并利用Caspases通路阻断结合免疫印迹法，证实PARP-1/AIF通路是重离子诱导神经细胞凋亡的重要途径之一。本项目以非Caspases的PARP-1/AIF凋亡通路为切入点，旨在探索重离子诱导神经细胞凋亡的新机制。

中文关键词： PARP-1；AIF；重离子辐射；神经细胞；凋亡

英文摘要： Poly(ADP-ribose) polymerase-1 (PARP-1),one of the most abundant nuclear, is highly conserved in eukaryotes.The gene mutation, deletion and overexpression of PARP-1 will directly impact the process of apoptosis. Apoptosis-inducing factor (AIF) is stimulated from excessive PARP activation to trigger non-Roles of caspases (caspase)-dependent apoptosis,which induces AIF translocation from the mitochondria to the nucleus. It has been proved that PARP-1/AIF pathway play a decisive role in ischemia-reperfusion-induced neuronal apoptosis. However,it remains unclear how to regulate heavy ion-caused apoptosis via interacting between PARP-1 and AIF. The project bulid the modle including mutant cell mediated by a lentiviral system for RNA interference and overexpression of target gene to identify the relationship between PARP-1 and AIF determined by Laser-scanning confocal microscopy (LSCM) or co-immunoprecipitation analysis after heavy-ion irradiation. We confirm whether PARP-1/AIF pathway is the important way to induce neuronal apoptosis in heavy-ion radiated cells through blocking Caspase-dependent pathway combined with Western blot method. Our study aim to investigate to explore a new mechanism of heavy ion-induced neuronal apoptosis in light of PARP-1/AIF-mediated caspase-independent apoptosis pathway.

英文关键词： PARP-1；AIF；Heavy ion irradiatoin；neverous cell；apoptosis