研究生: |
張薰勻 Chang, Hsur-Yun |
---|---|
論文名稱: |
AMP蛋白激酶的活化對金屬硫蛋白基因表現之影響 Effect of AMP-activated Protein Kinase Activation on Metallothionein Gene Expression |
指導教授: |
林立元
Lin, Lih-Yuan |
口試委員: | |
學位類別: |
碩士 Master |
系所名稱: |
生命科學暨醫學院 - 分子與細胞生物研究所 Institute of Molecular and Cellular Biology |
論文出版年: | 2009 |
畢業學年度: | 97 |
語文別: | 中文 |
論文頁數: | 47 |
中文關鍵詞: | 金屬硫蛋白 、能量缺失 |
外文關鍵詞: | AMPK, MT, energy-deprivation |
相關次數: | 點閱:4 下載:0 |
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金屬硫蛋白 (Metallothionein, MT)在生理上重要的功能為調節細胞內金屬的恆定性和對抗氧化壓力,而近幾年很多研究指出MT可能參與能量代謝的生理活動,但是仍沒有明確的機制。在研究中我們使用能量代謝抑制劑NaNB3B和2-deoxyglucose (2DG)處理HEK293細胞使之處於能量缺乏的情況,發現MT基因的表現受到抑制,且NaNB3B和2DG因阻斷細胞內ATP的生成而促進能量監督者AMPK的活性。由於AMPK調控細胞中能量的平衡,包括參與代謝的蛋白質或基因,於是我們測試NaNB3B是否透過活化AMPK而抑制MT基因的表現,我們利用Dominant-negative AMPK (DN-AMPK)與AMPK siRNA抑制AMPK的活性,發現當AMPK的活性被減低後,MT基因表現被NaNB3B抑制的情形減緩,故推測NaNB3B透過活化AMPK來調控MT基因的表現。當細胞遭受能量低迷的時候,活化的AMPK會藉由磷酸化受質來調控下游的代謝途徑與基因的表現,以維持細胞中的能量平衡,於是我們測試了與代謝有關的c-Myc和AMPK的受質Forkhead box O3 (FOXO3)是否參與在NaNB3B抑制MT基因表現的途徑中,結果顯示c-Myc和FOXO3均可能會影響MT基因表現,但不參與在NaNB3B活化AMPK而抑制MT基因表現的途徑。
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