ZEN對R2C細(xì)胞毒性作用中的內(nèi)質(zhì)網(wǎng)應(yīng)激機(jī)制研究
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本文關(guān)鍵詞: 玉米赤霉烯酮 內(nèi)質(zhì)網(wǎng)應(yīng)激 信號通路 差異蛋白 出處:《沈陽農(nóng)業(yè)大學(xué)》2016年碩士論文 論文類型:學(xué)位論文
【摘要】:玉米赤霉烯酮(Zearalenone,簡稱ZEN)是一種由鐮刀菌屬菌株產(chǎn)生的真菌毒素。它廣泛存在于飼料和谷物中,對玉米、小麥、大麥、燕麥、稻谷等具有很強(qiáng)的污染性。目前學(xué)術(shù)界的研究主要集中在ZEN對機(jī)體的生殖毒性、免疫毒性、細(xì)胞毒性、遺傳毒性,以及促癌促腫瘤等方面。氧化應(yīng)激是ZEN毒性作用的一個重要途徑。氧化應(yīng)激是指機(jī)體在接受各種有害刺激時,體內(nèi)高活性分子產(chǎn)生過多,氧化作用超出氧化物清除作用,促氧化系統(tǒng)與抗氧化系統(tǒng)間的動態(tài)平衡被打破,導(dǎo)致組織損傷的一種病理生理狀態(tài)。當(dāng)細(xì)胞出現(xiàn)氧化應(yīng)激等異常情況時,則可能出現(xiàn)內(nèi)質(zhì)網(wǎng)應(yīng)激。內(nèi)質(zhì)網(wǎng)應(yīng)激(又稱ER應(yīng)激)是指內(nèi)質(zhì)網(wǎng)穩(wěn)態(tài)發(fā)生紊亂的一種亞細(xì)胞器病理狀態(tài)。其本質(zhì)是內(nèi)質(zhì)網(wǎng)中未折疊或錯誤折疊的蛋白過度累積,從而激活一些適應(yīng)性的信號轉(zhuǎn)導(dǎo)通路而引起的應(yīng)激反應(yīng)。發(fā)生內(nèi)質(zhì)網(wǎng)應(yīng)激的標(biāo)志是:免疫球蛋白結(jié)合蛋白(BiP)和X盒結(jié)合蛋白1(XBP-1)表達(dá)上調(diào)。同時,CHOP和caspase-12等促凋亡分子,GADD34等促存活分子表達(dá)或者活化。這些物質(zhì)的表達(dá)或活化,可以判定是否發(fā)生ER應(yīng)激。我們知道,內(nèi)質(zhì)網(wǎng)應(yīng)激有三條信號通路,其標(biāo)志性分子是分別PERK, IRE-1, ATF6。通過這三種物質(zhì)的表達(dá)變化,可以判定ZEN引起的ER應(yīng)激是通過哪條通路實現(xiàn)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.
【學(xué)位授予單位】:沈陽農(nóng)業(yè)大學(xué)
【學(xué)位級別】:碩士
【學(xué)位授予年份】:2016
【分類號】:S859.87
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