量子点标记A型核纤层蛋白前体及在衰老中的应用研究

项目名称： 量子点标记A型核纤层蛋白前体及在衰老中的应用研究

项目编号： No.31201036

项目类型： 青年科学基金项目

立项/批准年度： 2013

项目学科： 遗传学与生物信息学、细胞生物学

项目作者： 吴都督

作者单位： 广东医学院

项目金额： 23万元

中文摘要： 核纤层蛋白前体A（prelamin A）的C末端不能被剪切或加工异常均导致衰老。Prelamin A 的C末端特异识别因子Narf参与其剪切并与细胞衰老有关。本项目拟利用水热合成法制备具有独特荧光性质的量子点，并通过抗体和抗原的强特异性结合及细胞对量子点的内吞作用标记Prelamin A和 Narf。同时采用细胞形态学结合流式细胞检测凋亡技术，研究量子点对细胞的毒性。通过对量子点标记的Narf与prelamin A作用的实时动态示踪，研究Narf与prelamin A的作用位点，以及蛋白运动对衰老的影响。同时利用荧光共振能量转移和同步荧光扫描技术，研究Narf与细胞受体prelamin A结合的精细行为，探索Narf与prelamin A相互作用规律。本项目研究结果将揭示Prelamin A和 Narf相互作用对衰老的影响。

中文关键词： 核纤核纤层蛋白前体 A；Narf 蛋白；量子点；早老症；

英文摘要： Modern society faces an increasing aging problem, and China is becoming an aging society at a very fast pace. Research on aging mechanisms leading to better diagnosis and prevention of age-related disease is increasingly important. However, human life span is relatively long making it difficult to study. Accelerated aging disorders in humans provide ideal model systems to understand the aging process since the accelerated aging syndromes usually recapitulate the normal aging process in many tissues. Our previous results indicate that if the C-terminal of prelamin A can not be cleaved or is cleaved abnormally，a premature aging syndrome will occur. The nuclear prelamin A specific recognition factor Narf participates in the cleavage process and is associated with cell senescence. Quantum dots (QDs) have been widely used as novel ?uorescent probes in biosensor and bioimaging due to their unique optical and electrical properties. In this program, we will use quantum, dot technology to label prelamin A and Narf and follow there localization both in proliferative and senescent cells in culture. We will also determine whether expression of prelamin A is cytotoxic, using Mitotracker staining and flow cytometry, and if co-expression of Narf reverses that toxicity. Furthermore, through dynamically folliwung the localizatio

英文关键词： Prelamin A；Narf protein；Quantum dots；Hutchinson-Gilford progeria syndrome；