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| ???org.dspace.app.webui.jsptag.ItemTag.dcfield??? | Value | Language |
|---|---|---|
| dc.contributor.advisor | 柯逢春(Fon-Chun Ke) | |
| dc.contributor.author | Ya-Hsun Shih | en |
| dc.contributor.author | 施雅薰 | zh_TW |
| dc.date.accessioned | 2021-06-13T03:18:42Z | - |
| dc.date.available | 2006-08-03 | |
| dc.date.copyright | 2006-08-03 | |
| dc.date.issued | 2006 | |
| dc.date.submitted | 2006-07-29 | |
| dc.identifier.citation | 參考文獻
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| dc.identifier.uri | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/31731 | - |
| dc.description.abstract | 摘要
細胞老化為一種不可逆且不再進行細胞複製之現象,因此和細胞凋亡並列為抑癌之機制,通常可以區分為增生性老化與早發性老化兩大類。於本實驗室先前的研究發現,由H2O2在WI38細胞株所引發的老化系統中,以免疫螢光染色的方式,可觀察到Hdm2分子會在細胞核中形成聚集 (foci) 現象。而本研究主要探討的主題,則是此一Hdm2 nuclear foci現象之形成是否與細胞老化有所關聯。因此除了原先前人所設立之以AOA,H2O2所誘發之老化系統之外,再多設立兩個不同來源的老化系統,試圖比較各個老化系統中Hdm2 nuclear foci之異同。另外,以H2O2 所誘發之細胞老化系統為主要模式,利用各式有可能干擾細胞老化的藥劑處理H2O2 所誘發之細胞老化系統,試圖藉由破壞Hdm2 nuclear foci的方式,檢驗細胞老化之現象是否受到影響,而建立兩者之因果聯繫,在眾多藥劑與H2O2共同處理的觀察中,我們得到三大類不同的結果;首先,利用Sirt1活化劑Resveratrol與Sirt1抑制劑Nicotinamide,p38抑制劑SB203580與 Erk 抑制劑PD98059分別與H2O2共同處理的結果,皆不影響Hdm2 nuclear foci現象之形成亦不影響細胞老化之染色。其次,利用PI3K抑制劑wortmannin可以阻斷H2O2所引發細胞老化結果,但不影響Hdm2 nuclear foci的形成。最後,在運用HDAC抑制劑TSA與H2O2的共同處理之下,發現Hdm2 nuclear foci之形態被破壞,且細胞老化的程度也有隨之降低的趨勢,因而暗示Hdm2 nuclear foci與細胞老化或許有某 種程度上之聯繫。 | zh_TW |
| dc.description.abstract | Abstract
Cellular senescence is an irreversible and permanent phenomenon of cell cycle arrest. Consequently, cellular senescence as well as apoptosis is recognized as tumor suppressive mechanism. Based on different inducing mechanism, cellular senescence could divide into two groups as replicative senescence and premature senescence. From previous studies, sublethal H2O2 concentration treatment could induce senescence in WI38 cell, and Hdm2 form the nuclear foci in the H2O2-induced senescent cells. In this study, we attempt to investigate whether Hdm2 nuclear foci formation correlate with cellular senescence phenomenon. Besides two established premature senescence systems induced by AOA and H2O2, we set up another two different senescence systems to compare Hdm2 nuclear foci phenomenon between systems. Otherwise, we use various potential senescence-interfering drugs co-treat with H2O2 and observe whether these drugs could disturb cellular senescence and Hdm2 nuclear foci formation corresponsively. we categorize our findings into 3 major groups : First, using Sirt1 activator Resveratrol and Sirt1 inhibitor Nicotinamide, p38 inhibitor SB203580 and Erk inhibitor PD98059 individually co-treat with H2O2 fails to block H2O2-induced senescence and fails to affect Hdm2 nuclear foci formation. Second, using PI3K inhibitor wortmannin could block H2O2-induced senescence, but did not disturb Hdm2 nuclear foci status. Finally, we found HDAC inhibitor TSA co-treat with H2O2 could destroy Hdm2 nuclear foci formation and lower cellular senescence ratio. This finding implies there might be some correlations between Hdm2 nuclear foci formation and cellular senescence phenomenon. | en |
| dc.description.provenance | Made available in DSpace on 2021-06-13T03:18:42Z (GMT). No. of bitstreams: 1 ntu-95-R92b43017-1.pdf: 3842051 bytes, checksum: bfe2cce7b375295201886e136e19c32a (MD5) Previous issue date: 2006 | en |
| dc.description.tableofcontents | 目錄
目錄 I 中文摘要 IV 英文摘要 IV 前言 1 壹、 細胞老化的歷史背景與性狀特徵 1 貳、 細胞老化與腫瘤形成 3 參、 細胞老化的分子機制 7 肆、 影響細胞老化系統之試劑與原理 16 伍、 實驗目的 21 材料方法 23 壹、 細胞培養與處理 23 貳、 Senescence Associated β-galatosidase stain 24 參、 細胞內涵物萃取 25 肆、 蛋白質電泳與西方轉漬法 27 伍、 免疫螢光染色法 28 陸、 免疫沈澱法 29 結果 31 壹、 不同的老化系統對於Hdm2 nuclear foci之比較 31 貳、 H2O2誘發之細胞老化系統中,Hdm2 foci形成時程之觀察 31 參、 不影響Hdm2 foci也不影響細胞老化之處理 32 肆、 不影響Hdm2 foci形成但影響細胞老化比例之處理 34 伍、 影響Hdm2 foci形成也影響細胞老化比例之處理 34 陸、 老化相關處理在U2OS細胞上之影響 35 柒、 Hdm2在各個系統中的存在方式 35 捌、 Hdm2與其相關分子在H2O2所誘發之老化系統中之修飾 36 玖、 P53高分子量處染色與H2O2所誘發之老化系統之關係 38 討論 39 壹、 不同的老化系統對於Hdm2 nuclear foci之探討 39 貳、 不同的處理方式對於Hdm2 nuclear foci影響之探討 40 參、 Hdm2與相關連蛋白質修飾狀態之探討 44 圖表 47 參考文獻 68 | |
| dc.language.iso | zh-TW | |
| dc.subject | 過氧化氫 | zh_TW |
| dc.subject | 細胞核內聚集現象 | zh_TW |
| dc.subject | 細胞老化 | zh_TW |
| dc.subject | cellular senescence | en |
| dc.subject | Nuclear foci | en |
| dc.subject | H2O2 | en |
| dc.title | Hdm2 Nuclear Foci 形成與細胞老化關係之探討 | zh_TW |
| dc.title | The Role of Hdm2 Nuclear Foci Formation in Cellular Senescence | en |
| dc.type | Thesis | |
| dc.date.schoolyear | 94-2 | |
| dc.description.degree | 碩士 | |
| dc.contributor.oralexamcommittee | 黃娟娟(Jiuan-Jiuan Hwang),李明亭(Ming-Ting Lee),黃火鍊(Fore-Lien Huang),蕭培文(Pei-Wen Hsiao) | |
| dc.subject.keyword | 細胞老化,過氧化氫,細胞核內聚集現象, | zh_TW |
| dc.subject.keyword | cellular senescence,H2O2,Nuclear foci, | en |
| dc.relation.page | 72 | |
| dc.rights.note | 有償授權 | |
| dc.date.accepted | 2006-07-30 | |
| dc.contributor.author-college | 生命科學院 | zh_TW |
| dc.contributor.author-dept | 分子與細胞生物學研究所 | zh_TW |
| Appears in Collections: | 分子與細胞生物學研究所 | |
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| ntu-95-1.pdf Restricted Access | 3.75 MB | Adobe PDF |
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