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| DC 欄位 | 值 | 語言 |
|---|---|---|
| dc.contributor.advisor | 黃楓婷(Feng-Ting Huang) | |
| dc.contributor.author | Jia-Xing Huang | en |
| dc.contributor.author | 黃家星 | zh_TW |
| dc.date.accessioned | 2021-07-10T22:03:45Z | - |
| dc.date.available | 2021-07-10T22:03:45Z | - |
| dc.date.copyright | 2021-01-05 | |
| dc.date.issued | 2020 | |
| dc.date.submitted | 2020-12-24 | |
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| dc.identifier.uri | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/77474 | - |
| dc.description.abstract | 運動被認為是可以預防許多的疾病，例如心血管疾病以及癌症，其中因運動而分泌的運動激素被認為扮演著重要的角色。Irisin 是一種在運動時被分泌的運動激素能透過棕化白色脂肪細胞成類棕色脂肪細胞而增加能量的消耗。許多文章也報導irisin能抑制許多種癌細胞的細胞增生。在本篇論文中我們純化帶有GST-tag的irisin重組蛋白並用來抑制神經膠質瘤細胞U-87 MG 的細胞增生， irisin能誘導p21的表現以及抑制cdc2磷酸化，而導致細胞於細胞週期G2/M期的數量上升。為了進一步探討irisin是透過何種訊息傳遞機制來抑制U-87 MG的細胞增生，於此論文中，利用針對訊息傳遞路徑多種專一性抗體及搭配抑制劑以西方墨點法分析。結果中發現irisin能結合在U-87 MG的細胞表面並結合到整合素αV受體。Irisin能經由整合素αV調節下游的訊息傳遞鏈，包括FAK和 JNK，然而AKT路徑可能是被其他受體所啟動。Irisin能誘導整合素αV下游的FAK/JNK路徑以及被其他受體啟動的AKT路徑提升Modaw20的表現，可能進而促進p21蛋白的表現以及氧化調節式的細胞死亡。儘管目前研究對irisin在癌細胞中作用的分子機制並不是完全了解，但irisin是極具有潛力治療癌症的藥物。 | zh_TW |
| dc.description.abstract | Several studies demonstrate that exercise is able to reduce disease incidence, such as cardiovascular diseases and cancer. The exercise-induced myokine is considered to play key mediator on cancer inhibition. Irisin is a myokine which is secreted by muscle cells during exercise, stimulating white adipose browning, to brown-like adipocytes, resulting in reducing the risk of obesity. Many studies find that irisin can inhibit the proliferation of several types of cancer cells. To investigate the irisin effects on cancer cells, the GST-tag human recombinant irisin was purified and utilized to inhibit cell proliferation of glioblastoma cell line, U-87 MG. Moreover, irisin-induced p21 upregulation and the inhibition of cdc2 might cause cell cycle G2/M phase arrest. To decipher the molecular mechanism that irisin reduced cell proliferation of U-87 MG cells, the irisin-induced signal transduction pathways was studied in this thesis. Our result showed that irisin bound to the live U-87 MG cells surface and specifically bind to the integrin αV receptors. The integrin αV receptor downstream signal transduction pathways, including FAK and JNK were regulated by irisin, but AKT pathway was activated by other receptors. Both the integrin αV activated FAK/JNK pathway and other receptors activated AKT pathway was able to upregulated the Modaw20 expression which might induce p21 expression and oxidative regulated cell death. Although the molecular mechanism of irisin effect on cancer cells is not completely clear yet, irisin is a potential therapeutic candidate for cancer therapy. | en |
| dc.description.provenance | Made available in DSpace on 2021-07-10T22:03:45Z (GMT). No. of bitstreams: 1 U0001-2412202015390600.pdf: 17039273 bytes, checksum: 866fb372803d0018f5d8aae0672115e4 (MD5) Previous issue date: 2020 | en |
| dc.description.tableofcontents | 謝詞 i 中文摘要 ii Abstract iii Abbreviations v Table of contents vi Chapter 1 Introduction 1 1.1 Exercise, myokine, and cancer 1 1.1.1 Exercise 1 1.1.2 Exercise-induced myokines 1 1.2 Irisin 2 1.2.1 Characteristics and biological function of irisin 2 1.2.2 Irisin effects on cancer 3 1.2.3 Integrin is irisin receptor 4 1.3 Glioblastoma 6 1.4 Cell cycle 7 1.5 Signal transduction 8 1.5.1 Signal transduction pathway 9 1.5.2 Irisin activates signal transduction pathway 10 1.6 Modaw20 12 1.7 Research purpose 14 Chapter 2 Materials and methods 16 2.1 Recombinant protein preparation 16 2.1.1 Irisin construct 16 2.1.2 Irisin induction 16 2.1.3 Irisin purification 16 2.2 Cell culture 17 2.3 Cell proliferation analysis 18 2.4 Cell cycle analysis 18 2.5 FITC-protein binding assay 19 2.5.1 Labeling FITC to protein 19 2.5.2 Binding of FITC-labeled protein to U-87 MG cells 20 2.5.3 Quantification of FITC-labeled protein bound to U-87 MG cells by flow cytometry 20 2.6 Cell lysates preparation 21 2.7 Protein electrophoresis and western blotting 21 2.8 Statistical analysis 22 Chapter 3 Results 23 3.1 Preparation of recombinant human irisin protein 23 3.2 Irisin inhibited cell proliferation of U-87 MG cells 23 3.3 Irisin induced cell cycle arrest by upregulation of p21 and phosphorylation of cdc2 24 3.4 Irisin bound to the cell surface of U-87 MG cells 25 3.5 Irisin inhibited cell proliferation via integrin αV receptor 26 3.6 Irisin activated signal transduction pathways in U-87 MG cells 28 3.7 Irisin regulated signal transduction pathways via integrin αV receptors in U-87 MG cells 30 3.8 Irisin induced the expression of Modaw20 via integrin downstream signal pathways 32 Chapter 4 Discussion 35 4.1 The GST tag on irisin 35 4.2 The irisin-induced cell cycle arrest in U-87 MG cells 36 4.3 Integrin αV is irisin receptors on U-87 MG cells 37 4.4 The irisin induced signal transduction pathways 38 4.5 Irisin induced Modaw20 expression in U-87 MG cells 40 Chapter 5 Summary and future prospects 43 References 45 Figures 52 Figure 1. Recombinant human irisin protein 53 Figure 2. Irisin inhibited the cell proliferation of U-87 MG cells 55 Figure 3. irisin induced cell cycle arrest at G2/M phase in U-87 MG cells 59 Figure 4. Irisin bound to the cell surface of live U-87 MG cells 62 Figure 5. Irisin reduced cell proliferation via binding to integrin αv receptors on U-87 MG cells 65 Figure 6. Irisin increased the phosphorylation of FAK, AKT and JNK and decreased the phosphorylation of AMPK 71 Figure 7. Irisin activated FAK and JNK pathways and inhibited the AMPK pathway, and these effects were reversed the inhibitor integrin αV receptors 75 Figure 8. Irisin induced Modaw20 expression via integrin αV receptors, AKT and JNK pathway 80 Figure 9. Schematic representation of irisin induced signal transduction pathways in U-87 MG cells contributed to cell proliferation inhibition 82 Appendixes 84 1. Antibodies 85 2. Chemicals and peptides 86 | |
| dc.language.iso | en | |
| dc.subject | 訊息傳遞 | zh_TW |
| dc.subject | 鳶尾素 | zh_TW |
| dc.subject | 多形性膠質母細胞瘤 | zh_TW |
| dc.subject | 細胞增生 | zh_TW |
| dc.subject | 細胞週期 | zh_TW |
| dc.subject | 整合素 | zh_TW |
| dc.subject | glioblastoma | en |
| dc.subject | signal transduction | en |
| dc.subject | integrin | en |
| dc.subject | cell cycle | en |
| dc.subject | cell proliferation | en |
| dc.subject | irisin | en |
| dc.title | 探討Irisin對人類神經膠質瘤細胞的訊號傳遞機制 | zh_TW |
| dc.title | Studies of the irisin-mediated signal transduction pathways in glioblastoma cells | en |
| dc.type | Thesis | |
| dc.date.schoolyear | 109-1 | |
| dc.description.degree | 碩士 | |
| dc.contributor.oralexamcommittee | 廖憶純(Yi-Chun Liao),陳彥榮(Edward Chern) | |
| dc.subject.keyword | 鳶尾素,多形性膠質母細胞瘤,細胞增生,細胞週期,整合素,訊息傳遞, | zh_TW |
| dc.subject.keyword | irisin,glioblastoma,cell proliferation,cell cycle,integrin,signal transduction, | en |
| dc.relation.page | 86 | |
| dc.identifier.doi | 10.6342/NTU202004457 | |
| dc.rights.note | 未授權 | |
| dc.date.accepted | 2020-12-25 | |
| dc.contributor.author-college | 生命科學院 | zh_TW |
| dc.contributor.author-dept | 生化科技學系 | zh_TW |
| 顯示於系所單位： | 生化科技學系 | |
文件中的檔案：
| 檔案 | 大小 | 格式 | |
|---|---|---|---|
| U0001-2412202015390600.pdf 未授權公開取用 | 16.64 MB | Adobe PDF |
系統中的文件，除了特別指名其著作權條款之外，均受到著作權保護，並且保留所有的權利。