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研究生:蘇義鈞
研究生(外文):Su Yi-Chun
論文名稱:鎘逆境造成細胞死亡與p53蛋白之相關性研究
論文名稱(外文):Roles of p53 cadmiunm-induced cell death
指導教授:林立元林立元引用關係
指導教授(外文):Lih-Yuan Lin
學位類別:碩士
校院名稱:國立清華大學
系所名稱:生命科學系
學門:生命科學學門
學類:生物學類
論文種類:學術論文
論文出版年:2002
畢業學年度:90
語文別:中文
論文頁數:61
中文關鍵詞:p53鎘逆境細胞死亡p21
外文關鍵詞:p53cadmiumG2/M arrestcell cyclehuman fibroblastp21MAPKs
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摘要
重金屬鎘是環境中常見的污染物質,在許多研究報告中指出,細胞受鎘處理後會造成細胞週期停滯和細胞進行程序性死亡。本論文主要是在探討當細胞受到鎘傷害後,p53蛋白在細胞中所扮演的角色。在實驗中我們發現當以30μM氯化鎘處理人類纖維母細胞(HF)後,可以偵測到細胞中的p53蛋白增加。然而誘發的p53蛋白並不會促進細胞程序性死亡的進行,也不會促使Bax及PIG3蛋白表現量增加。與p53缺失的HF細胞(HFE6)相較,在以鎘處理後HF細胞有較低程度的細胞死亡。當p53蛋白累積之後,會專一的誘導p21蛋白及MDM2蛋白表現,也發現p21蛋白的表現與G2/M期的細胞週期停滯有密切的相關性。我們進一步探討p53蛋白的累積是否與ERK、JNK和p38的活化有關。我們發現p53、JNK及p38三種蛋白之間,並沒有直接的關聯性存在。然而,當我們阻斷了ERK或p53其中一條訊號傳遞路徑,就會促使另一條路徑更活化。我們發現這兩條路徑似乎有互相補償的作用存在。在本篇論文我們認為p53蛋白在鎘處理的早期就會大量活化,且p53的表現與細胞週期停滯及細胞死亡有密切的關連性存在。

Abstract
Cadmium(Cd) is a common environmental contaminant. It has been reported that the Cd causes cell growth arrest and apoptosis. In this study we investigated the roles of p53 in cadmium-induced cell damage. When human fibroblast(HF) cells were treated with 30μM Cd, p53 increased in cells. However the increased p53 protein did not enhance apoptosis or the level of proapoptotic proteins such as Bax and PIG3. Comparing to the p53 deficient HF cells(HFE6), the HF cells showed a less degree of cell death after Cd treatment. After induction by Cd, p53 specifically stimulated its downstream targets, p21 and MDM2.The expression of p21 was related to G2/M arrest of HF cells. We further investigated whether the p53 accumulation is correlated with MAPKs activation in cadmium- treated cells. We found that JNK and p38 activation had no direct relationship with p53 protein. However, when the pathway to activate either ERK or p53 was blocked, the other one would be activated. This result indicated a compensation of two pathways during Cd treatment. In our study, we concluded that the Cd induce p53 accumulation in early phase, and the expression of p53 is closely related to cell cycle arrest, and cell death for the Cd treatment.

目次
中文摘要…………………………………………………………1
英文摘要…………………………………………………………2
序言………………………………………………………………3
材料與方法………………………………………………………15
結果………………………………………………………………20
討論………………………………………………………………30
參考資料…………………………………………………………36
附圖………………………………………………………………42

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黃琪惠(2001)鎘干擾逆境訊號分子胞內運送之共軛焦顯微分析。生命科學所論文

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