酸性成纤维细胞生长因子核转位序列敲除对其有丝分裂活性的影响

发布时间：2018-03-18 11:00

本文选题：酸性　切入点：纤维　出处：《吉林大学》2005年博士论文　论文类型：学位论文

【摘要】：酸性成纤维细胞生长因子(aFGF)在机体生长发育中发挥重要的有丝分裂作用。aFGF还具有非促分裂作用,如神经保护和心肌缺血保护等。aFGF在体外发挥非促分裂作用时,可能会产生由促分裂活性诱导的细胞转化,从而有引起细胞非正常增殖而可能产生的潜在危险。为了研究降低aFGF促分裂活性方法,从研究aFGF多肽链上的核转位序列与aFGF的信号途径的关联入手。通过人工敲除aFGF的该序列,制备了重组aFGF蛋白冻干粉(raFGF)。检测了两种蛋白的有丝分裂活性和受体酪氨酸激酶的信号途径。经比较分析认为,rFGF的促分裂活性明显低于waFGF。分析表明,raFGF的促分裂活性只与MAPK的级联有关,而不能够通过核转位途径发挥作用,而核转位序列在核转位途径中发挥重要作用。waFGF则可通过两种途径的协同作用发挥促分裂活性。对raFGF的细胞效应检测表明,raFGF具有维持细胞正常生存、避免发生细胞凋亡的作用。该研究结果在我们所做的动物实验中进一步得到的补充,即raFGF不但能够延长aFGF缺乏的新生大鼠的生存时间,而且还能够在一定程度上具有维持幼鼠正常神经系统功能的作用。而重要信号途径的丧失则有可能使raFGF的诱发细胞转化的可能性极小。
[Abstract]:Acidic fibroblast growth factor (aFGF) plays an important mitotic role in the growth and development of the body. AFGF also has non-mitogenic effects, such as neuroprotection and myocardial ischemia protection. Cell transformation may be induced by mitogenic activity, which may lead to abnormal cell proliferation. In order to study the method of reducing the mitogenic activity of aFGF, the correlation between the nuclear translocation sequence on aFGF polypeptide chain and the signal pathway of aFGF was studied. The recombinant aFGF protein freeze-dried powder was prepared. The mitotic activity and signal pathway of receptor tyrosine kinase of two proteins were detected. The results showed that the mitogenic activity of rFGF was significantly lower than that of waFGF. The results showed that the mitogenic activity of the two proteins was significantly lower than that of Waff FGF.The results showed that the mitogenic activity of the two proteins was significantly lower than that of Waff FGF. Only related to the cascades of MAPK, But not through nuclear translocation, The nuclear translocation sequence plays an important role in the nuclear translocation pathway. WaFGF can play a mitogenic role through the synergistic action of the two pathways. The detection of the cellular effect of raFGF shows that it can maintain the normal survival of the cells. The effect of cell apoptosis. The results of this study are further supplemented by our animal experiments, that is, raFGF can not only prolong the survival time of newborn rats lacking aFGF. Moreover, it can maintain the normal nervous system function of young rats to some extent, and the loss of important signal pathway may make the possibility of cell transformation induced by raFGF very small.
【学位授予单位】：吉林大学
【学位级别】：博士
【学位授予年份】：2005
【分类号】：R329

【共引文献】