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研究生:陳韋文
研究生(外文):Wei-Wen Chen
論文名稱:發炎對特定組織中甲硫胺酸合成酶影響之相關研究
論文名稱(外文):Inflammation causes tissue specific alterations of methionine synthase
指導教授:蔣恩沛
學位類別:碩士
校院名稱:國立中興大學
系所名稱:食品暨應用生物科技學系所
學門:醫藥衛生學門
學類:營養學類
論文種類:學術論文
畢業學年度:97
語文別:英文
論文頁數:49
中文關鍵詞:甲硫胺酸合成酶
外文關鍵詞:Methionine synthase
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背景 發炎作用對於單碳代謝系統中之特定酵素的影響尚未被詳細研究。
目的 我們的研究目的針對在體內中,慢性發炎對於甲硫胺酸合成酶之影響。
實驗設計與方法 我們比較慢性發炎病人和健康成人體內甲硫胺酸合成酶的表現。腫瘤壞死因子過度表現動物模型為將人類3’-修飾過之腫瘤壞死因子基因片段鑲嵌到老鼠體內,使動物體內過度表現腫瘤壞死因子,進而探討體內慢性發炎對於甲硫胺酸合成酶之影響。比較轉殖基因鼠和控制組中之甲硫胺酸轉甲基代謝情形。甲硫胺酸合成酶的活性和蛋白質表現分別利用放射線以及西方墨點法的方式測定。利用穩定放射性追蹤物質和氣相層析質譜儀,研究發炎對同半胱胺酸再甲基化及轉硫作用之代謝路徑走向之影響。
結果 發炎反應會降低在腫瘤壞死因子過度表現之動物體內之特定組織的甲硫胺酸合成酶之蛋白質表現量。穩定放射線追蹤實驗結果,在轉殖基因鼠中,依賴葉酸之同半胱胺酸再甲基化路徑,相較於控制組有偏低現象。此外,轉殖基因母鼠肝臟中,同半胱胺酸轉硫路徑運行情形則是高於控制組。嘌呤以及嘧啶之重新合成,在轉殖基因鼠中的特定組織表現明顯低於控制組。
結論 發炎反應對於針對個別性別之特定組織中的甲硫胺酸合成酶有不同之影響。
Background. The impact of inflammation on specific enzymes involved in the one-carbon metabolism is unclear.
Objective of the study was to investigate the impact of chronic inflammation on 5-methyltetrahydrofolate-homocysteine methyltransferase in vivo.
Design and Methods. The expression of 5-methyltetrahydrofolate-homocysteine methyltransferase in patients with chronic inflammation and in healthy controls were compared. The TNF-α transgenic mouse carries a 3’-modified human Tumor Necrosis Factor (TNF) transgene that exhibits upregulated TNF expression and progressive development of severe inflammation was used to study the impacts of chronic inflammation on 5-methyltetrahydrofolate-homocysteine methyltransferase in vivo. Methionine transmethylation metabolites were compared between the TNF-α transgenic and wild type mice. The activity and the protein quantity of 5-methyltetrahydrofolate-homocysteine methyltransferase were determined by radioisotope enzymatic assay and western blot. The effect of TNF overexpression on homocysteine remethylation and transsulfuration metabolic fluxes were investigated using stable isotopic tracers and Gas Chromatography/Mass Spectrometry.
Results. TNF overexpression decreased 5-methyltetrahydrofolate-homocysteine methyltransferase protein in a tissue specific manner in our mouse model. Data from the labeling experiments suggested that folate-dependent homocysteine remethylation were reduced in transgenic mice compared to that of the wild type mice. Hepatic homocysteine transsulfuration flux of TNF-α transgenic mice appeared to be induced compared to the wild-type mice only in the female mice. De novo purine and pyrimidine synthesis were significantly reduced in specific tissues.
Conclusion Inflammation altered 5-methyltetrahydrofolate-homocysteine methyltransferase in a tissue and gender specific manner.
List of abbreviation.. i
中文摘要..............ii
ABSTRACT.............iii
Introduction...........1
METHERIALS AND METHODS.3
RESULTS................8
DISCUSSIONS...........12
REFERENCES............46
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