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研究生:陳怡安
研究生(外文):Chen, Yi-An
論文名稱:鋅離子對人類支氣管上皮細胞PTEN蛋白質的分布及其功能之影響
論文名稱(外文):Effect of zinc ions on the cellular localization and function of PTEN in human bronchial epithelial cells
指導教授:林立元林立元引用關係
指導教授(外文):Lin, Lih-Yuan
學位類別:碩士
校院名稱:國立清華大學
系所名稱:分子與細胞生物研究所
學門:生命科學學門
學類:生物科技學類
論文種類:學術論文
論文出版年:2014
畢業學年度:102
語文別:中文
論文頁數:65
中文關鍵詞:人類支氣管上皮細胞腫瘤抑制基因細胞核轉錄因子
外文關鍵詞:BEAS-2BPTENNF-κBZinc
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中文摘要

PTEN是調控PI3K/Akt訊號傳遞、抑制細胞存活及過度增生不可或缺的重要蛋白質。已知鋅離子可影響人類支氣管上皮細胞(BEAS-2B)中的PTEN蛋白質的表現,本篇實驗進一步的探討在BEAS-2B中,鋅離子是如何對PTEN蛋白質造成影響及其生物效應。首先我們利用西方墨點法證實鋅離子確實會影響PTEN與報導中和PTEN降解有關的蛋白質表現。由於先前研究指出PTEN上K13及K289的泛素化會造成PTEN降解。因此我們將該位置被突變的PTEN送入BEAS-2B中,但結果顯示,單泛素化位置被破壞的PTEN仍會受到鋅離子的影響,鋅離子會增加IKK的活性並降低IκB的量,給予PTEN下游的Akt抑制劑並無法改變鋅離子對NFκB造成的影響。最後我們也觀察鋅對PTEN及NFκB的影響與死亡途徑是否有關,然而我們的實驗結果顯示鋅並不會誘導細胞走向凋亡(Apoptosis)或壞死(Necrosis)。近年來的文獻顯示鋅離子確實參與許多重要的訊息調控,然而,對鋅在生理及毒理方面的角色仍不清楚。本篇研究我們推測鋅會透過一種非細胞凋亡的訊號途徑影響PTEN及NFkB蛋白質的表現及分布情形,但詳細的作用機制尚未明瞭,而這些未知的生理現象可提供我們未來作更深入探討的方向。


Abstract

PTEN is a tumor suppressor protein that inhibits cell growth and viability by modulating the PI3K/AKT signaling pathway. Zinc has been reported to cause PTEN degradation in the airway epithelium. In this study, we further investigate how zinc impact on the PTEN protein and bioeffect in BEAS-2B cells. First, we showed that zinc can suppress the level of PTEN. In previous studies, Reportedly, K13 and K289 are two major monoubiquitination sites that related to PTEN stability. We expressed PTENK13/K289E mutant into BEAS-2B cells and found that BEAS-2B cell was still sensitive to Zinc treatment. Noticeably, zinc activates IKK activity and reduces IκB level in the cells. Administration of Akt inhibitor did not block the zinc-induced IKK activation. Finally, we also examined whether cell viability is associated with the zinc-induced PTEN degradation. The result shows that zinc induce BEAS-2B cell death which is not related to apoptosis, necrosis or autophagy. There is increasing evidence showing that zinc plays a key role in many signaling pathway. However, the underlying mechanisms are poorly understood. Here we assessed the effect of zinc on PTEN and NFκB through a non apoptotic cell death, and the detailed mechanisms needs further investigation.



目錄
中文摘要..................................................3
英文摘要..................................................4
縮寫表....................................................5
中英對照表................................................6
緒論......................................................7
材料與方法...............................................15
結果.....................................................24
討論.....................................................35
參考文獻.................................................41
附圖.....................................................52

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