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研究生:賴秋萍
研究生(外文):Ciou-Ping Lai
論文名稱:曼氏血吸蟲感染過程中小鼠肝組織蛋白質N-linked醣化作用變化之分析
論文名稱(外文):Analysis of progressive changes in the protein N-linked glycosylation profile of mouse liver during the course of Schistosoma mansoni infection
指導教授:李金木李金木引用關係邱繼輝邱繼輝引用關係
指導教授(外文):Kin-Mu LeeKay-Hooi khoo
學位類別:碩士
校院名稱:國立陽明大學
系所名稱:寄生蟲學研究所
學門:醫藥衛生學門
學類:醫學學類
論文種類:學術論文
論文出版年:2004
畢業學年度:92
語文別:中文
論文頁數:101
中文關鍵詞:曼氏血吸蟲醣化作用
外文關鍵詞:N-glycansialylatiom
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血吸蟲症(schistosomiasis)乃血吸蟲屬寄生蟲所引起的蠕蟲寄生性疾病,在熱帶地區約有二億人口受到感染。血吸蟲病的病徵主要因為蟲卵沉積於宿主之肝臟及組織,導致許多白血球團團圍住蟲卵,造成肉芽腫病變。本研究主要應用質譜儀技術分析來探討小鼠肝組織在寄生蟲感染期間醣化反應之變化。在小鼠感染曼氏血吸蟲後十八週期間,包括初期、急性期,及慢性期,分別從肝組織萃取醣蛋白,利用醣解酵素釋出N- glycans後,經由化學衍生及外切酵素酶水解配合的應用,以質譜儀及串聯式質譜儀分析鑑定其整體性的醣質表現圖譜。研究結果顯示,小鼠感染曼氏血吸蟲後其肝組織發生異常醣化現象在形成肉芽腫期間為最明顯。尤以complex type醣鏈在表現比例上明顯比high mannose type上升許多。值得注意的是末端的唾液酸化(sialylation)修飾中出現NeuAc取代的現象。在生合成過程中,NeuGc的產生,主要藉由CMP-NeuAc hydroxylase的酵素反應將CMP- NeuAc 修飾轉變成CMP -NeuGc。經由RT-PCR實驗顯示CMP-NeuAc hydroxylase在小鼠受染後表現量逐漸下降,因而導致所見的唾液酸化(sialylation)的變化。本論文研究結果顯示當小鼠受感染後其肝組織所表現異常的sialylation醣化現象可能與特殊酵素的表現調控有關。
Schistosomiasis is a helminthic parasitic disease caused by blood flukes of the genus Schistosoma, afflicting about 200 million individuals in the tropics. The pathology of the disease is associated with egg deposition in the liver and intestines and is characterized by the formation of granulomas developing around viable egg, and become surrounded by leukocytes. In this work, mass spectrometry(MS)- based methodologies are employed to map the changes in the glycosylation profile of the liver tissue as a consequence of parasitic infection. Glycoproteins were extracted from liver of BALB/c mice infected with Schistosoma manson during a 18-week infectious cycle, which includes early stage, acute stage, and chronic stage. N-glycans were released, chemically derivatized, sequential exoglycosidase digested and subjected to MS mapping and MS/MS sequencing. The results show that there is a drastic change in the glycomic map as the normal liver developed into granuloma. There was a significant increase in the proportion of complex type glycan relative to high mansone type. Importantly, the sialylation pattern was changed from one that was mainly N- glycolylneuraminic acid(NeuGc) to one that was dominated by N- acetylylneuraminic acid (NeuAc). This change in the amount of N-glycan substituted with NeuGc or NeuAc was shown by RT-PCR to be a consequence of drcreased expression of a hydroxylase converting CMP- NeuAc into CMP- NeuGc. This model of a liver infection suggests that the protein N-glycosylation profile of mouse liver is characterized by a dynamic sialylation process being modulated by the altered expression of a specific enzyme during parasitic infection.
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