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完整後設資料紀錄
DC 欄位 | 值 | 語言 |
---|---|---|
dc.contributor.advisor | 陳進庭 | |
dc.contributor.author | Yu-Hsin Lin | en |
dc.contributor.author | 林郁欣 | zh_TW |
dc.date.accessioned | 2021-06-13T01:18:58Z | - |
dc.date.available | 2008-07-27 | |
dc.date.copyright | 2007-07-27 | |
dc.date.issued | 2007 | |
dc.date.submitted | 2007-07-19 | |
dc.identifier.citation | 曾嘉儀 (2004) 五胺基酮戊酸光動力效應誘發PC12細胞粒線體傷害的相關生物效應探討。碩士論文。國立台灣大學口腔生物學研究所,台北。
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dc.identifier.uri | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/29790 | - |
dc.description.abstract | 粒線體在細胞中是重要的產能工廠,同時也調控著細胞內的代謝、離子平衡、老化及死亡等生理機制。因此,粒線體的功能若發生異常,在細胞的生理功能上往往會發生失序現象,甚至導致細胞死亡。對於神經細胞而言,粒線體的功能對於其生長及分化更是扮演著重要的角色。目前已有研究發現,粒線體功能喪失與氧化壓力會造成神經細胞退化及死亡,因而造成神經退化方面之疾病。五-氨基酮戊酸光動力效應 (ALA-PDT) 為一新興癌症治療方式,其作用為能夠選擇性地作用於粒線體產生氧化壓力,因而導致細胞的死亡。在本研究中我們利用五-氨基酮戊酸光動力效應做為一可特定造成粒線體傷害的工具,並採用老鼠嗜鉻細胞瘤 (Rat Pheochromocytoma cells, PC12 cells) 做為類似神經細胞之模式細胞株,探討PC12細胞在五-氨基酮戊酸光動力效應造成粒線體光傷害後,所誘發的訊息傳遞機轉及其死亡路徑為何?研究結果顯示,經由五-氨基酮戊酸光動力效應導致的粒線體受損造成PC12細胞生長週期停止,這一現象和p53、p21、p27等細胞週期調控因子表現量的增加有關。而在此一致壓效應下,發現PC12細胞的死亡伴隨著caspase活化,但抑制caspase的活性卻不影響其死亡,初步推論autophagy可能為其主要死亡途徑。在其他相關訊息調控因子中,我們發現細胞內MAPKs成員ERK、JNK、p38均被活化,其中JNK及p38的活化與促進細胞的死亡有關。另一方面,粒線體受損誘導PC12細胞活化Akt及AMPK (AMP-activated protein kinase),這些分子的活化與細胞死亡機制的調控有關。 | zh_TW |
dc.description.abstract | Mitochondria are intracellular organelles with a variety of vital functions, such as the provision of energy, cell metabolism, ion homeostasis, ageing, and death. Many evidences suggest that mitochondrial dysfunction induced by oxidative stress results in neurodegeneration and neural death. 5- aminolevulinic acid mediated photodynamic therapy (ALA-PDT), which is a novel therapy for neoplasia, can specifically induce oxidative stress at mitochondria. In this study, ALA-PDT was used as a tool to damage the mitochondria of Rat Pheochromocytoma cells (PC12 cells). Then, the signaling cascades related to the damage repaired and death mechanism were addressed. Here we show that, in PC12 cells, mitochondrial dysfunctions induced by ALA-PDT suppress the cell progression cycle at G0/G1 phase. This cell-cycle arrest correlates with the increased expression of p53, p21 and p27. Although activation of caspase-3, -9 was found in PC12 cells following lethal dose of ALA-PDT, cell death was found in a caspase-independent manner. Further evidences revealed that autophagy might be the main death mechanism involved in ALA-PDT induced mitochondrial damage. Furthermore, activation of Akt, AMPK and MAPKs families (ERK, JNK and p38) were found in response to ALA-PDT induced mitochondrial photodamages. The cell survival will increase after the inhibition of JNK, p38 and AMPK. However, the activation of Akt were found to protect cells from ALA-PDT induced cell death. | en |
dc.description.provenance | Made available in DSpace on 2021-06-13T01:18:58Z (GMT). No. of bitstreams: 1 ntu-96-R94b47401-1.pdf: 10836762 bytes, checksum: 3c84c30188b9f085e68e9978fda13b20 (MD5) Previous issue date: 2007 | en |
dc.description.tableofcontents | 口試委員會審定書……………………………………………………i
中文摘要………………………………………………………………ii 英文摘要…………………………………………………………… iii 目錄………………………………………………………………… iv 縮寫表……………………………………………………………… v 第一章 緒論 1.1 粒線體………………………………………………………… 1 1.2 老鼠嗜鉻細胞瘤……………………………………………… 2 1.3 細胞死亡機轉………………………………………………… 3 1.4 細胞週期調控………………………………………………… 5 1.5 p53 protein………………………………………………… 8 1.6 MAPKs………………………………………………………… 8 1.7 Akt…………………………………………………………… 9 1.8 AMPK…………………………………………………………… 9 1.9 五胺基酮戊酸光動力效應…………………………………… 10 1.10 研究動機與目的…………………………………………… 13 第二章 材料與方法 2.1 藥品與儀器…………………………………………………… 15 2.2 供試細胞株…………………………………………………… 17 2.3 細胞計數……………………………………………………… 18 2.4 光動力處理…………………………………………………… 18 2.5 細胞存活率測定……………………………………………… 19 2.6 細胞凋亡測定………………………………………………… 19 2.7 LDH assay…………………………………………………… 21 2.8 流式細胞儀 (flow cytometry) 測定細胞週期…………… 21 2.9 西方點墨法 (Western blot) ……………………………… 22 2.10 統計方法…………………………………………………… 24 第三章 結果 3.1 粒線體受損對PC12細胞生長的影響……………………… 25 3.2 PC12細胞粒線體受光傷害後所導致之死亡機轉………… 27 3.3 粒線體受損對於PC12細胞內訊息調控之影響…………… 31 第四章 討論……………………………………………………… 39 第五章 結論……………………………………………………… 46 附圖一~十一……………………………………………………… 48 Figure 1- 19…………………………………………………… 59 參考文獻………………………………………………………… 81 | |
dc.language.iso | zh-TW | |
dc.title | 粒線體功能異常所引發PC12細胞生長與死亡之相關訊息傳遞機制探討 | zh_TW |
dc.title | Studies of mitochondria-dysfunction induced signal transduction mechanism involved in the growth and death of PC12 cells | en |
dc.type | Thesis | |
dc.date.schoolyear | 95-2 | |
dc.description.degree | 碩士 | |
dc.contributor.oralexamcommittee | 黃慶璨,許瑞祥,林淑萍,揚啟伸 | |
dc.subject.keyword | 粒線體,PC12細胞,細胞凋亡,自噬作用,五-氨基酮戊酸,光動力效應, | zh_TW |
dc.subject.keyword | mitochondria,PC12 cells,apoptosis,autophagy,5-Aminolevulinic acid,photodynamic treatment, | en |
dc.relation.page | 89 | |
dc.rights.note | 有償授權 | |
dc.date.accepted | 2007-07-19 | |
dc.contributor.author-college | 生命科學院 | zh_TW |
dc.contributor.author-dept | 微生物與生化學研究所 | zh_TW |
顯示於系所單位: | 微生物學科所 |
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