接头蛋白Nck影响FGF2诱导的细胞保护机制研究-生物化学与分子生物学专业论文.docxVIP

华 华 中 科 技 大 学 硕 士 学 位 论 文 II II 作用下，通过影响 RasGAP 来调控 Ras 的活性进而调节 PI3K/AKT 通路，最终决定 神经细胞的生存能力。本文的研究结果为进一步深入揭示 FGF2促神经细胞的生存机 制奠定了基础，同时有望为相关神经退行性疾病的治疗提供新的理论基础和药物研 发的新靶点。 关键词：FGF2；非催化性蛋白激酶 Nck；衣霉素；内质网应激；鼠神经元干细胞 C17.2 III III Abstract? The survival of neuron is frequently used as the pathological feature in various neurodegenerative diseases and death of a great many neurons can seriously influence nervous system function. Therefore, it`s of great significance to explore the resistance and adaptability mechanisms in nervous system under pathological state. Recent researches have found that endoplasmic reticulum stress signal pathway has close relationship with central nervous system diseases, including neurodegenerative diseases and regional cerebral ischemia. Fibroblast growth factor 2 or basic fibroblast growth factor is a multiple-effect factor, having close relationship with neurodegenerative diseases, can promote cell proliferation and growth, induce cell differentiation and so forth. Evidences have confirmed that increasing in FGF2 expression after brain injury can promote neuron survival through PI3K/AKT and ERK activation. There is no related report whether FGF2 affects ER stress induced apoptosis. Adaptor protein Nck is a kind of non-catalytic protein kinase and widely conducts activated receptor tyrosine kinases and downstream proteins signal transduction, however there is little known about mechanism of Nck in FGF2 induced protective effect , which needs further clarified. This study used murine nervous stem cell C17.2 as research object and tunicamycin, which is a chemical induction of ER stress, to imitate pathological condition and figure out the protective effect of fibroblast growth factor 2 and roles Nck plays in. Through detecting related proteins in signaling pathway, we observed that FGF2 notably inhibited apoptotic protein PARP cleavage induced by Tun.However overexpression of downstream protein Nck could antagonize FGF2-mediated effect. FG