PARP-1活性参与NF-κB的基因转录调控的机制研究

发布时间：2019-03-31 12:02

【摘要】：PARP-1是一种富含在细胞核中的酶,DNA损伤能引起其高度活化,利用NAD+作为供体转移多聚ADP核糖(PAR)到受体蛋白。PARP-1在维持基因组完整性和控制细胞周期具有重要作用。近期研究发现它参与了很多基因转录的调节。机体对抗微生物感染一个主要机制是产生ROS,而ROS极其容易导致宿主细胞DNA损伤。微生物侵染机体后宿主细胞Toll-like受体活化是天然免疫的重要途径。许多免疫相关的促炎或抗炎的基因的转录调节都与转录因子NF-κB的活化相关。但在感染性炎症进程中,PARP-1的活化机制,以及PARP-1如何在活化后参与基因转录的调控,尚缺乏深入探讨与揭示。我们的工作旨在探讨TLR4识别的配体LPS刺激Ana-1小鼠巨噬细胞是否引发PARP-1的活化?LPS活化PARP-1参与的基因转录的主要机制?PARP-1如何与NF-κB相互作用参与转录调控?研究结果将有助于进一步理解PARP-1在感染性炎症进程中参与基因转录调控的机制,及PARP-1活化后在胞内整合的信号传导途径。
[Abstract]:PARP-1 is a kind of enzyme rich in nucleus. DNA damage can induce its high activation. NAD is used as donor to transfer ADP ribose (PAR) to receptor protein. PARP-1 plays an important role in maintaining genomic integrity and controlling cell cycle. Recent studies have found that it is involved in many gene transcription regulation. One of the main mechanisms of anti-microbial infection is the production of ROS, and ROS is very easy to cause DNA damage in host cells. Activation of Toll-like receptor in host cells after microbial infection is an important pathway of innate immunity. Transcriptional regulation of many immune-related pro-inflammatory or anti-inflammatory genes is associated with the activation of transcription factor NF- kappa B. However, in the process of infectious inflammation, the mechanism of PARP-1 activation and how PARP-1 participates in the regulation of gene transcription after activation have not been thoroughly discussed and revealed. Our aim is to explore whether the activation of PARP-1 by TLR4-recognized ligand LPS-stimulated Ana-1 mouse macrophages, the main mechanism of LPS-activated PARP-1 gene transcription, and how PARP-1 interacts with NF- 魏 B to participate in transcriptional regulation. The results will be helpful to further understand the mechanism of PARP-1 involved in gene transcription regulation in infectious inflammatory process and the signal transduction pathway of PARP-1-activated integration in cells.
【学位授予单位】：东北师范大学
【学位级别】：硕士
【学位授予年份】：2011
【分类号】：R363

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