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ZEN对R2C细胞毒性作用中的内质网应激机制研究

发布时间:2018-01-29 06:17

  本文关键词: 玉米赤霉烯酮 内质网应激 信号通路 差异蛋白 出处:《沈阳农业大学》2016年硕士论文 论文类型:学位论文


【摘要】:玉米赤霉烯酮(Zearalenone,简称ZEN)是一种由镰刀菌属菌株产生的真菌毒素。它广泛存在于饲料和谷物中,对玉米、小麦、大麦、燕麦、稻谷等具有很强的污染性。目前学术界的研究主要集中在ZEN对机体的生殖毒性、免疫毒性、细胞毒性、遗传毒性,以及促癌促肿瘤等方面。氧化应激是ZEN毒性作用的一个重要途径。氧化应激是指机体在接受各种有害刺激时,体内高活性分子产生过多,氧化作用超出氧化物清除作用,促氧化系统与抗氧化系统间的动态平衡被打破,导致组织损伤的一种病理生理状态。当细胞出现氧化应激等异常情况时,则可能出现内质网应激。内质网应激(又称ER应激)是指内质网稳态发生紊乱的一种亚细胞器病理状态。其本质是内质网中未折叠或错误折叠的蛋白过度累积,从而激活一些适应性的信号转导通路而引起的应激反应。发生内质网应激的标志是:免疫球蛋白结合蛋白(BiP)和X盒结合蛋白1(XBP-1)表达上调。同时,CHOP和caspase-12等促凋亡分子,GADD34等促存活分子表达或者活化。这些物质的表达或活化,可以判定是否发生ER应激。我们知道,内质网应激有三条信号通路,其标志性分子是分别PERK, IRE-1, ATF6。通过这三种物质的表达变化,可以判定ZEN引起的ER应激是通过哪条通路实现的。
[Abstract]:Zearalenone (Zen) is a mycotoxin produced by Fusarium strains. It is widely found in fodder and cereals for corn, wheat, barley, and oats. At present, the research of ZEN mainly focuses on the reproductive toxicity, immune toxicity, cytotoxicity and genetic toxicity of ZEN to the body. Oxidative stress is an important pathway of toxic effect of ZEN. Oxidative stress refers to the excessive production of highly active molecules in the body when the body is exposed to various harmful stimuli. Oxidation is more than oxide scavenging, and the dynamic balance between oxidation promoting system and antioxidant system is broken, resulting in a pathophysiological state of tissue injury. Endoplasmic reticulum stress (ER stress). A suborganelle pathological state in which the homeostasis of the endoplasmic reticulum occurs. Its essence is the excessive accumulation of unfolded or misfolded proteins in the endoplasmic reticulum. The markers of endoplasmic reticulum stress are immunoglobulin binding protein (BiP) and X-box binding protein (XBP-1). Upregulation. At the same time. Survivor-promoting molecules such as CHOP and caspase-12, such as GADD34, are expressed or activated. The expression or activation of these substances can be used to determine whether ER stress occurs. Endoplasmic reticulum stress has three signaling pathways, and its signature molecules are PERK, IRE-1, ATF6.Through the changes of expression of these three substances. The ER stress caused by ZEN can be determined by which pathway.
【学位授予单位】:沈阳农业大学
【学位级别】:硕士
【学位授予年份】:2016
【分类号】:S859.87

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