基础稳态重链铁蛋白和可诱导重链铁蛋白在肿瘤坏死因子诱导L929细胞死亡中的不同作用

发布时间：2018-05-30 18:45

本文选题：重链铁蛋白 + 动态离子库　；参考：《厦门大学》2007年博士论文

【摘要】： 肿瘤坏死因子-α(Tumor necrosis factor-α,TNF-α)是一种细胞因子,它能诱导某些细胞系经半胱天冬酶(caspase)依赖的细胞死亡途径死亡(细胞凋亡);与此同时,它也能够诱导另外一些细胞系通过非半胱天冬酶依赖的途径死亡(细胞坏死)。本文应用逆转录病毒随机插入介导基因失活的方法,以鼠纤维原细胞L929为材料,筛选在TNF诱导细胞死亡过程中起重要作用的基因。我们获得一株TNF抗性细胞株,其重链铁蛋白基因被破坏。用TNF处理此细胞株,细胞内的动态铁离子库(labile iron pool,LIP)上升幅度很小。我们同时发现,在野生型L929细胞中,TNF诱导LIP上升主要是通过细胞内储存的铁离子来补充。动态铁离子库(LIP)在TNF诱导细胞产生活性氧(Reactive oxygen species,ROS)和活性氧依赖的细胞死亡过程中起重要作用。在重链铁蛋白基因被破坏的细胞(Fer~(mut))中,重链铁蛋白减少导致细胞内储存的铁离子减少,最终使TNF诱导的细胞内LIP上升幅度变小。与其它细胞不同,L929细胞内的重链铁蛋白基因不能被TNF诱导表达。用TNF诱导表达系统在L929细胞中异位表达重链铁蛋白,TNF处理后,细胞内LIP上升被抑制,因LIP上升导致的细胞内ROS的产生也被抑制,进而抑制细胞死亡。因此,LIP在TNF诱导细胞死亡过程中起决定作用。它是基础稳态重链铁蛋白促进TNF诱导的细胞死亡和可诱导重链铁蛋白抑制TNF诱导的细胞死亡的一个共同的衡量标准。
[Abstract]:Tumor necrosis factor - alpha (Tumor necrosis factor- alpha, TNF- a) is a cytokine that can induce some cell lines to die by cell death pathway dependent on caspase (caspase). At the same time, it can also induce other cell lines to pass through non caspase dependent pathway death (cell necrosis). The method of random insertion of a retrovirus to mediate gene inactivation, using the mouse fibroblast cell L929 as the material, was used to screen the genes that play an important role in the process of TNF induced cell death. We obtained a TNF resistant cell strain, whose heavy chain ferritin gene was destroyed. The dynamic iron ion Library (labile iron poo in the cell) was treated with TNF. L, LIP) rose very little. We also found that in wild type L929 cells, TNF induced LIP increase mainly through the iron ions stored in the cells. The dynamic iron ion Library (LIP) plays an important role in TNF induced cells producing living oxygen (Reactive oxygen species, ROS) and reactive oxygen dependent cell death. In heavy chain iron eggs In the cell (Fer~ (MUT)) of the white gene, the reduction of heavy chain ferritin leads to the reduction in the iron ions stored in the cells, and eventually the increase in the intracellular LIP induced by TNF is smaller. The heavy chain ferritin gene in L929 cells can not be induced by TNF, unlike other cells. The TNF induced expression system is ectopic expression of heavy chain in L929 cells. After TNF treatment, the intracellular LIP rise was inhibited and the production of ROS in cells caused by LIP was inhibited and then cell death was inhibited. Therefore, LIP plays a decisive role in TNF induced cell death. It is the basic stable heavy chain ferritin to promote TNF induced cell death and induce heavy chain ferritin to inhibit TNF induced by TNF. A common measure of cell death.
【学位授予单位】：厦门大学
【学位级别】：博士
【学位授予年份】：2007
【分类号】：R341

【共引文献】