發(fā)布時(shí)間：2018-02-13 07:43

  本文關(guān)鍵詞： 誘導(dǎo)型一氧化氮合酶 X-box結(jié)合蛋白1 CAT ELISA 轉(zhuǎn)錄調(diào)控 啟動(dòng)子　出處：《重慶醫(yī)科大學(xué)》2006年博士論文　論文類(lèi)型：學(xué)位論文

【摘要】： 研究目的 真核細(xì)胞中一氧化氮(NO)作為第二信使和神經(jīng)遞質(zhì)發(fā)揮著多種不同的功能,具有廣泛的生物學(xué)效應(yīng)和抗病毒作用,參與機(jī)體的多種生理及病理過(guò)程,其對(duì)疾病發(fā)生及發(fā)展的影響是近年來(lái)研究的熱點(diǎn)。誘導(dǎo)型一氧化氮合酶(inducible nitric oxide synthase,iNOS)是產(chǎn)生一氧化氮的限速酶,廣泛分布于機(jī)體內(nèi),一切影響iNOS活性的因素及影響iNOS基因轉(zhuǎn)錄、翻譯的因素都會(huì)影響一氧化氮的生成,其中iNOS基因轉(zhuǎn)錄過(guò)程的調(diào)控是一氧化氮產(chǎn)量控制的主要因素。本研究首先運(yùn)用噬菌體表面展示技術(shù)篩選出12種iNOS基因的調(diào)節(jié)蛋白,X-盒結(jié)合蛋白1(X-box binding protein1,XBP1)是其中一種iNOS基因的調(diào)節(jié)蛋白,他是CREB/ATF家族一個(gè)重要的轉(zhuǎn)錄因子,通過(guò)與真核基因啟動(dòng)子區(qū)域中順式作用元件發(fā)生特異性相互作用、或者與其他相關(guān)蛋白質(zhì)之間發(fā)生相互作用,激活或抑制轉(zhuǎn)錄,調(diào)節(jié)基因的表達(dá),并通過(guò)整合這些不同的調(diào)節(jié)機(jī)制,激發(fā)無(wú)數(shù)基因的表達(dá)模式。為揭示真核細(xì)胞中iNOS基因的轉(zhuǎn)錄調(diào)控機(jī)制、反式作用因子X(jué)BP1對(duì)iNOS基因的調(diào)節(jié)作用,我們進(jìn)一步針對(duì)篩選出的調(diào)節(jié)蛋白XBP1進(jìn)行生物學(xué)功能的初步研究,對(duì)XBP1進(jìn)行細(xì)胞內(nèi)定位;篩選和構(gòu)建XBP1與其他蛋白質(zhì)間相互作用的連鎖圖,為闡明XBP1基因和iNOS基因的轉(zhuǎn)錄調(diào)節(jié)機(jī)制提供實(shí)驗(yàn)依據(jù),為進(jìn)一步揭示NO在肝細(xì)胞中的信號(hào)傳遞機(jī)制奠定理論基礎(chǔ)。 研究方法
[Abstract]:Research purpose. Nitric oxide (no) in eukaryotic cells, as a second messenger and neurotransmitter, plays many different functions, has a wide range of biological and antiviral effects, and participates in various physiological and pathological processes of the body. Inducible nitric oxide synthase (inducible nitric oxide synthase iNOS) is a rate-limiting enzyme that produces nitric oxide and is widely distributed in the body. All factors that affect the activity of iNOS and the transcription of iNOS gene are involved in this study. Translation factors affect the production of nitric oxide, The regulation of the transcription of iNOS gene is the main factor to control the production of nitric oxide. In this study, 12 iNOS gene regulatory proteins (1 X box binding protein 1 X box binding protein 1 XBP1) were screened by phage display technique. The regulatory protein of the iNOS gene, He is an important transcription factor in the CREB/ATF family that activates or inhibits transcription by interacting specifically with cis-acting elements in the eukaryotic promoter region or with other related proteins. In order to reveal the transcriptional regulation mechanism of iNOS gene in eukaryotic cells, the transactional factor XBP1 regulates the expression of iNOS gene by integrating these different regulatory mechanisms. We further studied the biological function of the screened regulatory protein XBP1, and carried out intracellular localization of XBP1. We screened and constructed a linkage map of the interaction between XBP1 and other proteins. In order to elucidate the transcriptional regulation mechanism of XBP1 gene and iNOS gene, and lay a theoretical foundation for further revealing the signal transduction mechanism of no in hepatocytes. Research method
【學(xué)位授予單位】：重慶醫(yī)科大學(xué)
【學(xué)位級(jí)別】：博士
【學(xué)位授予年份】：2006
【分類(lèi)號(hào)】：R346

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