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| DC 欄位 | 值 | 語言 |
|---|---|---|
| dc.contributor.advisor | 許秉寧(Ping-Ning Hsu) | |
| dc.contributor.author | Yi-Tzu Lin | en |
| dc.contributor.author | 林怡孜 | zh_TW |
| dc.date.accessioned | 2021-05-12T09:32:54Z | - |
| dc.date.available | 2018-08-30 | |
| dc.date.available | 2021-05-12T09:32:54Z | - |
| dc.date.copyright | 2018-08-30 | |
| dc.date.issued | 2018 | |
| dc.date.submitted | 2018-08-07 | |
| dc.identifier.citation | Ashktorab, H., Dashwood, R.H., Dashwood, M.M., Zaidi, S.I., Hewitt, S.M., Green, W.R., Lee, E.L., Daremipouran, M., Nouraie, M., Malekzadeh, R., et al. (2008). H. pylori-induced apoptosis in human gastric cancer cells mediated via the release of apoptosis-inducing factor from mitochondria. Helicobacter 13, 506-517.
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| dc.identifier.uri | http://tdr.lib.ntu.edu.tw/handle/123456789/1123 | - |
| dc.description.abstract | 胃幽門螺旋桿菌(Helicobacter pylori)是一種世界上常見的細菌感染源之一，主要棲息在人體胃部，並且已被發現與許多胃部疾病的發生有關，例如胃炎、胃潰瘍、黏膜層淋巴瘤、胃癌。其中，過去研究發現感染胃幽門螺旋桿菌的表皮細胞其細胞凋亡的程度增加與胃幽門螺旋桿菌所導致的胃部病變有關。先前實驗室的研究顯示，TRAIL能誘導感染胃幽門螺旋桿菌的胃上皮細胞進行大量細胞凋亡，進一步我們發現胃幽門螺旋桿菌透過負調控Akt的磷酸化程度使得AIP4蛋白活性增加，導致重要的調控蛋白FILPs進行泛素化降解，進而細胞無法阻礙TRAIL receptor下游死亡複合物的形成，導致胃上皮細胞容易被TRAIL誘導細胞凋亡。於此篇我們更利用AIP4基因剃除後發現AIP4分子的確參與在調控胃幽門螺旋桿菌誘導之TRAIL細胞凋亡之訊息傳導途徑中。此外，在此篇研究中我們也探討了胃幽門螺旋桿菌如何調控Akt的磷酸化，我們發現胃幽門螺旋桿菌會降低Akt的上游分子mTOR的表現量，並且我們發現隨著感染時間增長，mTOR的表現量降低與Akt去磷酸化程度、FLIPs的表現量降低呈現正相關，因此我們推測mTOR可能也參與在胃幽門螺旋桿菌所誘發的胃上皮細胞TRAIL敏感性提高。我們同時也利用mTOR抑制劑與mTOR siRNA轉染證明若於胃上皮細胞抑制mTOR活性則會導致細胞內FLIPs表現量下降且同時誘導細胞對TRAIL敏感度提升，此現象如同模擬胃幽門螺旋桿菌感染的情況。再者，我們過度表現mTORC2於人類胃上皮細胞後發現藉由於細胞內增強mTOR-Akt-FLIP訊號傳遞路徑可以使人類胃上皮細胞抵禦胃幽門螺旋桿菌所誘發之TRAIL引起的細胞凋亡。在此篇研究中我們定義出mTOR分子於胃幽門螺旋桿菌的致病機制中扮演重要角色，並且提供其成為將來治療感染胃幽門螺旋桿菌的分子標的之可能性。 | zh_TW |
| dc.description.abstract | Helicobacter pylori (H. pylori) is one of the most common pathogens that inhabits in human stomach, which has been known for being related to amounts of gastric disease such as gastritis, peptic ulcers, gastric MALT lymphomas and gastric cancer. It has been reported that the etiology of H. pylori is associated with the enhancement of cell apoptosis in gastric epithelial cells. Previous study in our laboratory has shown that H. pylori confers susceptibility to TRAIL-mediated apoptosis in human gastric epithelial cells through decreased Akt phosphorylation, which results in activating the AIP4 and leads to FLIPs degradation sequentially. In this study, we have further demonstrated that knockout of AIP4 in AGS cells mitigated H. pylori-induced TRAIL-mediated apoptosis, which has clarified that Akt-AIP4-FLIPs pathway participated in H. pylori-induced TRAIL apoptosis signaling. Besides, in order to investigate how H. pylori regulates Akt phosphorylation state, we have searched for the upstream molecular of Akt and found mTOR expression decreased while H. pylori co-cultured with gastric epithelial cells. Moreover, we found that the augmentation of mTOR-Akt pathway by overexpressing mTORC2 in gastric epithelial cells reduced H.pylori-induced TRAIL-apoptosis signaling. In this study, we address the role of mTOR in H. pylori-induced TRAIL apoptosis signaling and provide a new insight for the pathogenesis of H. pylori. | en |
| dc.description.provenance | Made available in DSpace on 2021-05-12T09:32:54Z (GMT). No. of bitstreams: 1 ntu-107-R05449002-1.pdf: 2466977 bytes, checksum: 22fe0170077fed6daf135061f32e1d9c (MD5) Previous issue date: 2018 | en |
| dc.description.tableofcontents | 口試委員會審定書 i
誌謝 ii 中文摘要 iii Abstract iv Introduction 1 1. Helicobacter pylori (H. pylori) 1 2. Pathogenesis of H. pylori 2 3. TRAIL-mediated apoptosis 4 4. H. pylori enhances TRAIL-induced apoptosis signaling in gastric epithelial cells 6 5. The Akt pathway in regulation of FLIPs expression 6 6. mTOR signaling in regulation of FLIPs expression 8 Rationales 10 Materials and Methods 11 Results 25 I. H. pylori enhanced the apoptosis of AGS cells while treat with TRAIL, and phosphorylation of Akt as well as FLIPs expression in AGS cells decreased concurrently. 25 II. The expression of FLIPs was decreased and enhanced TRAIL-mediated apoptosis in AGS cells after knockdown of Akt. 26 III. Knockout of AIP4 reduced H. pylori-induced TRAIL-mediated caspase-8 activation. 27 IV. mTOR expression was decreased after H. pylori co-cultured. 28 V. Inhibition of mTOR reduced the expression of FLIPs and induced TRAIL-mediated apoptosis in AGS cells. 29 VI. Enhancement of mTOR-Akt signaling pathway reduced H. pylori-induced TRAIL-mediated apoptosis signaling. 30 VII. H. pylori-induced autophagy could be attenuated while enhanced mTOR-Akt signaling pathway in AGS cells. 31 Discussion 33 I. H. pylori-induced TRAIL-mediated apoptosis through inhibiting the intracellular mTOR-Akt signaling pathway. 33 II. H. pylori downregulated FLIPs expression through reducing Akt phosphorylation. 36 III. H. pylori downregulated FLIPs expression through Akt-independent mechanisms. 40 IV. The upstream regulation of mTORC2 activity and the possible pathway for H. pylori to disrupt the mTORC2 activity in AGS cell lines. 41 Conclusion 44 References 45 Figures 55 | |
| dc.language.iso | en | |
| dc.subject | mTOR | zh_TW |
| dc.subject | 胃幽門螺旋桿菌 | zh_TW |
| dc.subject | 細胞凋亡 | zh_TW |
| dc.subject | TRAIL | zh_TW |
| dc.subject | mTOR | en |
| dc.subject | TRAIL | en |
| dc.subject | apoptosis | en |
| dc.subject | Helicobacter pylori | en |
| dc.title | 研究mTOR分子於胃幽門螺旋桿菌調控胃上皮細胞對TRAIL細胞凋亡訊息傳導所扮演之角色 | zh_TW |
| dc.title | Study the role of mTOR in regulation of Helicobacter pylori-induced TRAIL apoptosis signaling in Human gastric epithelial cells | en |
| dc.type | Thesis | |
| dc.date.schoolyear | 106-2 | |
| dc.description.degree | 碩士 | |
| dc.contributor.oralexamcommittee | 朱清良(Ching-Liang chu),謝世良(Shie-Liang Hsieh),吳明賢(Ming-Shiang Wu) | |
| dc.subject.keyword | 胃幽門螺旋桿菌,細胞凋亡,TRAIL,mTOR, | zh_TW |
| dc.subject.keyword | Helicobacter pylori,apoptosis,TRAIL,mTOR, | en |
| dc.relation.page | 69 | |
| dc.identifier.doi | 10.6342/NTU201802646 | |
| dc.rights.note | 同意授權(全球公開) | |
| dc.date.accepted | 2018-08-08 | |
| dc.contributor.author-college | 醫學院 | zh_TW |
| dc.contributor.author-dept | 免疫學研究所 | zh_TW |
| 顯示於系所單位： | 免疫學研究所 | |
文件中的檔案：
| 檔案 | 大小 | 格式 | |
|---|---|---|---|
| ntu-107-1.pdf | 2.41 MB | Adobe PDF | 檢視/開啟 |
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