請用此 Handle URI 來引用此文件：
http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/42522完整後設資料紀錄
| DC 欄位 | 值 | 語言 |
|---|---|---|
| dc.contributor.advisor | 張震東(Geen-Dong Chang) | |
| dc.contributor.author | Yu-Ting Weng | en |
| dc.contributor.author | 翁于婷 | zh_TW |
| dc.date.accessioned | 2021-06-15T01:15:25Z | - |
| dc.date.available | 2011-07-31 | |
| dc.date.copyright | 2009-07-31 | |
| dc.date.issued | 2009 | |
| dc.date.submitted | 2009-07-28 | |
| dc.identifier.citation | Bence, N.F., Sampat, R.M., and Kopito, R.R. (2001). Impairment of the ubiquitin-proteasome system by protein aggregation. Science 292, 1552-1555.
Boyault, C., Zhang, Y., Fritah, S., Caron, C., Gilquin, B., Kwon, S.H., Garrido, C., Yao, T.P., Vourc'h, C., Matthias, P., and Khochbin, S. (2007). HDAC6 controls major cell response pathways to cytotoxic accumulation of protein aggregates. Genes Dev 21, 2172-2181. Cai, C., Masumiya, H., Weisleder, N., Matsuda, N., Nishi, M., Hwang, M., Ko, J.K., Lin, P., Thornton, A., Zhao, X., et al. (2009). MG53 nucleates assembly of cell membrane repair machinery. Nat Cell Biol 11, 56-64. Cecarini, V., Gee, J., Fioretti, E., Amici, M., Angeletti, M., Eleuteri, A.M., and Keller, J.N. (2007). Protein oxidation and cellular homeostasis: Emphasis on metabolism. Biochim Biophys Acta 1773, 93-104. Coorssen, J.R., Schmitt, H., and Almers, W. (1996). Ca2+ triggers massive exocytosis in Chinese hamster ovary cells. EMBO J 15, 3787-3791. Davies, K.J. (2000). Oxidative stress, antioxidant defenses, and damage removal, repair, and replacement systems. IUBMB Life 50, 279-289. Davies, K.J. (2001). Degradation of oxidized proteins by the 20S proteasome. Biochimie 83, 10. de Ruijter, A.J., van Gennip, A.H., Caron, H.N., Kemp, S., and van Kuilenburg, A.B. (2003). Histone deacetylases (HDACs): characterization of the classical HDAC family. Biochem J 370, 737-749. Eskelinen, E.L., Schmidt, C.K., Neu, S., Willenborg, M., Fuertes, G., Salvador, N., Tanaka, Y., Lullmann-Rauch, R., Hartmann, D., Heeren, J., et al. (2004). Disturbed cholesterol traffic but normal proteolytic function in LAMP-1/LAMP-2 double-deficient fibroblasts. Mol Biol Cell 15, 3132-3145. Folk, J.E. (1983). Mechanism and basis for specificity of transglutaminase-catalyzed epsilon-(gamma-glutamyl) lysine bond formation. Adv Enzymol Relat Areas Mol Biol 54, 1-56. Halliwell, B., and Gutteridge, J.M. (1984). Oxygen toxicity, oxygen radicals, transition metals and disease. Biochem J 219, 1-14. Han, R., and Campbell, K.P. (2007). Dysferlin and muscle membrane repair. Curr Opin Cell Biol 19, 409-416. Haroon, Z.A., Hettasch, J.M., Lai, T.S., Dewhirst, M.W., and Greenberg, C.S. (1999). Tissue transglutaminase is expressed, active, and directly involved in rat dermal wound healing and angiogenesis. FASEB J 13, 1787-1795. Heiss, A., DuChesne, A., Denecke, B., Grotzinger, J., Yamamoto, K., Renne, T., and Jahnen-Dechent, W. (2003). Structural basis of calcification inhibition by alpha 2-HS glycoprotein/fetuin-A. Formation of colloidal calciprotein particles. J Biol Chem 278, 13333-13341. Huang, H.C., Liu, Y.C., Liu, S.H., Tzang, B.S., and Lee, W.C. (2002). Geldanamycin inhibits trichostatin A-induced cell death and histone H4 hyperacetylation in COS-7 cells. Life Sci 70, 1763-1775. Hubbert, C., Guardiola, A., Shao, R., Kawaguchi, Y., Ito, A., Nixon, A., Yoshida, M., Wang, X.F., and Yao, T.P. (2002). HDAC6 is a microtubule-associated deacetylase. Nature 417, 455-458. Huynh, C., Roth, D., Ward, D.M., Kaplan, J., and Andrews, N.W. (2004). Defective lysosomal exocytosis and plasma membrane repair in Chediak-Higashi/beige cells. Proc Natl Acad Sci U S A 101, 16795-16800. Idone, V., Tam, C., and Andrews, N.W. (2008a). Two-way traffic on the road to plasma membrane repair. Trends Cell Biol 18, 552-559. Idone, V., Tam, C., Goss, J.W., Toomre, D., Pypaert, M., and Andrews, N.W. (2008b). Repair of injured plasma membrane by rapid Ca2+-dependent endocytosis. J Cell Biol 180, 905-914. Izagirre, U., Angulo, E., Wade, S.C., ap Gwynn, I., and Marigomez, I. (2009). Beta-glucuronidase and hexosaminidase are marker enzymes for different compartments of the endo-lysosomal system in mussel digestive cells. Cell Tissue Res 335, 441-454. Kabeya, Y., Mizushima, N., Ueno, T., Yamamoto, A., Kirisako, T., Noda, T., Kominami, E., Ohsumi, Y., and Yoshimori, T. (2000). LC3, a mammalian homologue of yeast Apg8p, is localized in autophagosome membranes after processing. EMBO J 19, 5720-5728. Kamada, Y., Funakoshi, T., Shintani, T., Nagano, K., Ohsumi, M., and Ohsumi, Y. (2000). Tor-mediated induction of autophagy via an Apg1 protein kinase complex. J Cell Biol 150, 1507-1513. Kawai, Y., Wada, F., Sugimura, Y., Maki, M., and Hitomi, K. (2008). Transglutaminase 2 activity promotes membrane resealing after mechanical damage in the lung cancer cell line A549. Cell Biol Int 32, 928-934. Kiffin R, B.U., Cuervo AM (2006). Oxidative stress and autophagy. Antioxid Redox Signal 8, 11. Kovacs, J.J., Murphy, P.J., Gaillard, S., Zhao, X., Wu, J.T., Nicchitta, C.V., Yoshida, M., Toft, D.O., Pratt, W.B., and Yao, T.P. (2005). HDAC6 regulates Hsp90 acetylation and chaperone-dependent activation of glucocorticoid receptor. Mol Cell 18, 601-607. McNeil, P.L., and Kirchhausen, T. (2005). An emergency response team for membrane repair. Nat Rev Mol Cell Biol 6, 499-505. Mellgren, R.L., and Huang, X. (2007). Fetuin A stabilizes m-calpain and facilitates plasma membrane repair. J Biol Chem 282, 35868-35877. Mizushima, N. (2007). Autophagy: process and function. Genes Dev 21, 2861-2873. Mizushima, N., and Yoshimori, T. (2007). How to interpret LC3 immunoblotting. Autophagy 3, 542-545. Pandey, U.B., Nie, Z., Batlevi, Y., McCray, B.A., Ritson, G.P., Nedelsky, N.B., Schwartz, S.L., DiProspero, N.A., Knight, M.A., Schuldiner, O., et al. (2007). HDAC6 rescues neurodegeneration and provides an essential link between autophagy and the UPS. Nature 447, 859-863. Petiot, A., Ogier-Denis, E., Blommaart, E.F., Meijer, A.J., and Codogno, P. (2000). Distinct classes of phosphatidylinositol 3'-kinases are involved in signaling pathways that control macroautophagy in HT-29 cells. J Biol Chem 275, 992-998. Ravikumar, B., Vacher, C., Berger, Z., Davies, J.E., Luo, S., Oroz, L.G., Scaravilli, F., Easton, D.F., Duden, R., O'Kane, C.J., and Rubinsztein, D.C. (2004). Inhibition of mTOR induces autophagy and reduces toxicity of polyglutamine expansions in fly and mouse models of Huntington disease. Nat Genet 36, 585-595. Reddy, A., Caler, E.V., and Andrews, N.W. (2001). Plasma membrane repair is mediated by Ca(2+)-regulated exocytosis of lysosomes. Cell 106, 157-169. Schafer, C., Heiss, A., Schwarz, A., Westenfeld, R., Ketteler, M., Floege, J., Muller-Esterl, W., Schinke, T., and Jahnen-Dechent, W. (2003). The serum protein alpha 2-Heremans-Schmid glycoprotein/fetuin-A is a systemically acting inhibitor of ectopic calcification. J Clin Invest 112, 357-366. Schmelzle, T., and Hall, M.N. (2000). TOR, a central controller of cell growth. Cell 103, 253-262. Shepard, B.D., Joseph, R.A., Kannarkat, G.T., Rutledge, T.M., Tuma, D.J., and Tuma, P.L. (2008). Alcohol-induced alterations in hepatic microtubule dynamics can be explained by impaired histone deacetylase 6 function. Hepatology 48, 1671-1679. Shiflett, S.L., Kaplan, J., and Ward, D.M. (2002). Chediak-Higashi Syndrome: a rare disorder of lysosomes and lysosome related organelles. Pigment Cell Res 15, 251-257. Spiro, R.G. (1960). Studies on fetuin, a glycoprotein of fetal serum. I. Isolation, chemical composition, and physiochemical properties. J Biol Chem 235, 2860-2869. Stadtman, E.R., and Levine, R.L. (2000). Protein oxidation. Ann N Y Acad Sci 899, 191-208. Steinhardt, R.A., Bi, G., and Alderton, J.M. (1994). Cell membrane resealing by a vesicular mechanism similar to neurotransmitter release. Science 263, 390-393. Sudhof, T.C., and Rizo, J. (1996). Synaptotagmins: C2-domain proteins that regulate membrane traffic. Neuron 17, 379-388. Sugita, S., and Sudhof, T.C. (2000). Specificity of Ca2+-dependent protein interactions mediated by the C2A domains of synaptotagmins. Biochemistry 39, 2940-2949. Tang, G., Yue, Z., Talloczy, Z., Hagemann, T., Cho, W., Messing, A., Sulzer, D.L., and Goldman, J.E. (2008). Autophagy induced by Alexander disease-mutant GFAP accumulation is regulated by p38/MAPK and mTOR signaling pathways. Hum Mol Genet 17, 1540-1555. Togo, T. (2006). Disruption of the plasma membrane stimulates rearrangement of microtubules and lipid traffic toward the wound site. J Cell Sci 119, 2780-2786. Tucci, P., Cione, E., Perri, M., and Genchi, G. (2008). All-trans-retinoic acid induces apoptosis in Leydig cells via activation of the mitochondrial death pathway and antioxidant enzyme regulation. J Bioenerg Biomembr 40, 315-323. Valenzuela-Fernandez, A., Cabrero, J.R., Serrador, J.M., and Sanchez-Madrid, F. (2008). HDAC6: a key regulator of cytoskeleton, cell migration and cell-cell interactions. Trends Cell Biol 18, 291-297. Verdel, A., Curtet, S., Brocard, M.P., Rousseaux, S., Lemercier, C., Yoshida, M., and Khochbin, S. (2000). Active maintenance of mHDA2/mHDAC6 histone-deacetylase in the cytoplasm. Curr Biol 10, 747-749. Wada, F., Hasegawa, H., Nakamura, A., Sugimura, Y., Kawai, Y., Sasaki, N., Shibata, H., Maki, M., and Hitomi, K. (2007). Identification of substrates for transglutaminase in Physarum polycephalum, an acellular slime mold, upon cellular mechanical damage. FEBS J 274, 2766-2777. Xie, Z., and Klionsky, D.J. (2007). Autophagosome formation: core machinery and adaptations. Nat Cell Biol 9, 1102-1109. Zhang, Y., Li, N., Caron, C., Matthias, G., Hess, D., Khochbin, S., and Matthias, P. (2003). HDAC-6 interacts with and deacetylates tubulin and microtubules in vivo. EMBO J 22, 1168-1179. Zhang, Z., Yamashita, H., Toyama, T., Sugiura, H., Omoto, Y., Ando, Y., Mita, K., Hamaguchi, M., Hayashi, S., and Iwase, H. (2004). HDAC6 expression is correlated with better survival in breast cancer. Clin Cancer Res 10, 6962-6968. 蔡秉村 (2008) 上皮細胞細胞膜修補之訊息傳遞研究。國立台灣大學生化科學研究所碩士論文。 | |
| dc.identifier.uri | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/42522 | - |
| dc.description.abstract | 細胞因為機械壓力或外力所造成短細胞膜傷害，在細胞膜受傷後，細胞內會接觸到細胞外相對氧化的環境，造成胞內蛋白質被氧化形成蛋白質聚集(protein aggregates)。此外，細胞外Ca2+大量進入細胞內，促進液泡融合(vesicles fusion)或胞吐作用(exocytosis)於損傷處形成膜狀區塊，防止細胞內物質持續溢出細胞。之後細胞會進行胞吞作用(endocytosis)產生內吞體(endosome)移除細胞膜上的修補區域，而促進細胞膜的組成復原。目前還沒有人提出細胞膜傷害後，蛋白質聚集、膜狀區塊以及內吞體是如何被清除。
本篇論文中，利用磁珠滾動的方式大規模傷害細胞的細胞膜後，發現在滾珠後四小時會誘發自噬作用。若3-methyladenine (3-MA)抑制自噬作用則會使滾珠後細胞的存活率下降，顯示自噬作用可輔助細胞膜修補來增加細胞的存活率。此外，我們發現HDAC6不參與此類的自噬作用，而且此類的自噬作用並不幫助清除polyubiquitined proteins。由於蛋白質聚集、膜狀區塊以及內吞體沒有polyubiquitination，應該不是透過ubiquitin的途徑來降解，而且它們的分子量都很大，因此細胞滾珠後誘發的自噬作用可能可以幫助清除蛋白質聚集、膜狀區塊以及內吞體的機制。 | zh_TW |
| dc.description.abstract | Transient plasma membrane disruptions commonly occur in cells that experience mechanical stress or external force. From what we have known, disruption of the plasma membrane would lead to the exposure of the cell interior to the external oxidizing environment and change the oxidation state of proteins in cells. These oxidized proteins would become extensively aggregated or cross-linked and attach to the disrupted plasma membrane. Furthermore, extracellular Ca2+ would enter cells, promoting vesicle fusion and exocytosis to form membrane patches that prevent cell contents from spilling out of cells. Afterward, damaged cells proceed to endocytosis and the formation of endosomes that promote the replacement of wound areas in plasma membrane. Protein aggregates, membrane patches, and endosomes that occur during plasma membrane disruption might cause cell stress. At present, it remains unclear how protein aggregates, membrane patches, and endosomes are eliminated in cells after membrane damage.
Here, the results suggest that membrane damage at 4 hour after magnetic beads rolling is able to induce autophagy. By blocking autophagy with 3-methyladenine (3-MA), cell viability decreased after beads rolling. These results imply that autophagy participates in membrane repair. Moreover, we found that polyubiquitination and HDAC6 were not involved in the autophagic process following membrane damage and repair. Since ubiquitination plays a minimal role, autophagy, an alternative pathway caused by beads rolling, might help to eliminate protein aggregates, membrane patches and endosomes. | en |
| dc.description.provenance | Made available in DSpace on 2021-06-15T01:15:25Z (GMT). No. of bitstreams: 1 ntu-98-R96b46010-1.pdf: 5657416 bytes, checksum: 38630426896a1754e9fb7bbdf5e3bf61 (MD5) Previous issue date: 2009 | en |
| dc.description.tableofcontents | 目錄
口試委員會審定書 誌謝 Ⅰ 中文摘要 Ⅱ 英文摘要 Ⅲ 縮寫表 Ⅷ 第一章 前言 第一節 細胞膜修補(membrane repair) 1-1 細胞膜修補步驟 1 1-2 感應細胞膜受傷及液泡聚集 1 1-3 液泡融合和胞吐作用形成膜狀區塊 2 1-4 胞吞作用移除細胞膜上傷口 3 1-5 Tissue transglutaminase(TG)與細胞膜修補 3 1-6 Calcium phosphate binding protein-胎兒蛋白(Fetuin A) 4 與細胞膜修補 第二節 自噬作用(Autophagy)和自噬體(Autophagosome) 2-1 自噬作用的定義與形式 5 2-2 參與自噬體的蛋白質及marker 5 2-3 自噬作用藉由HDAC6抑制神經退化疾病 6 第三節 研究動機與目的 8 第二章 材料與方法 第一節 細胞培養 9 第二節 細胞滾珠 9 第三節 cell lysate的萃取 9 第四節 SDS聚丙烯胺凝膠電泳[Sodium Dodecyl Sulfate－ 9 PolyAcrylamide Gel Electrophoresis (SDS-PAGE)] 第五節 西方點墨法 (Western Blotting) 10 第六節 免疫螢光染色 (Immunofluorescence Staining) 11 第七節 建構EGFP-LC3 plasmid 7-1 引子(Primer)的設計 12 7-2 聚合酶連鎖反應 (Polymerase Chain Reaction, PCR) 12 7-3 洋菜膠電泳分析 (Agarose Gel Electrophoresis) 12 7-4 DNA去鹽 (Desalt) 13 7-5 DNA片段磷酸化 13 7-6 洋菜膠回收 13 7-7 PGEMT vector與DNA的接合反應(Ligation)和E. Coli細胞轉型 14 (Transformation) 7-8 菌落聚合酶連鎖反應 (Colony-PCR) 14 7-9 E. Coli液態培養 15 7-10 質體DNA(Plasmid)的抽取 15 7-11 核酸限制酶切割 (Digestion of Restriction Enzyme) 15 7-12 EGFP-C1 vector與DNA的接合反應 (Ligation) 15 第八節 細胞轉染 (Transfection) 16 第九節 MTT assay 16 第十節 藥物處理 17 第三章 實驗結果 第一節 細胞膜傷害後引起自噬反應 18 第二節 細胞膜傷害後引起適量的自噬作用可增加細胞存活率 19 第三節 HDAC6不參與細胞膜傷害後引起的自噬作用 20 第四節 細胞膜傷害後引起自噬作用不幫助清除polyubiquitined 21 proteins 第五節 細胞膜傷害後HDAC6立即減少並非進入細胞核內 22 第四章 討論 第一節 自噬作用與膜狀區塊和內吞體 23 第二節 自噬作用與氧化壓力 23 第三節 自噬作用與HDAC6 24 第四節 自噬作用與p38MAPK 24 第五節 HDAC6大量溢出細胞 25 第五章 圖表 圖1 細胞膜受傷後Fetuin A聚集在細胞膜表面隨後被清除 26 圖2 磁珠滾動傷害細胞的細胞膜後四小時誘發自噬作用 27 圖3 磁珠滾動傷害細胞的細胞膜後四小時利用免疫螢光染色觀察 28 autophagosome 圖4 磁珠滾動傷害細胞的細胞膜後四小時利用細胞轉染EGFP-LC3B 29 plasmid觀察autophagosome 圖5 磁珠滾動傷害細胞的細胞膜後四小時利用細胞轉染EGFP-LC3B plasmid及 30 LC3B免疫螢光染色觀察自噬體 圖6 3-methyladenine(3-MA)抑制自噬作用與Rapamycin促進自噬作用對 31 細胞膜傷害後A431-Ⅲ細胞存活的影響 圖7 HDAC6對細胞膜傷害後引起自噬作用的影響 33 圖8 HDAC6不參與細胞膜傷害後引起的自噬作用 35 圖9 細胞膜傷害後引起自噬作用不幫助清除polyubiquitined proteins 37 圖10 細胞膜傷害後HDAC6立即減少並非進入細胞核內 39 第六章 參考文獻 40 第七章 附錄 附錄1 Mitsugumin53 (MG53)可感應細胞膜受傷並促進細胞內液泡聚集 46 附錄2 Dysferlin可幫助液泡移動到細胞膜受傷的地方並促進液泡融合 47 附錄3 溶酶體(lysosome)是主要參與膜狀區塊形成的液泡 48 附錄4 液泡在細胞膜受傷的位置進行融合和胞吐作用，形成膜狀區塊 49 附錄5 Macroautophagy的形成 50 附錄6 mTOR pathway 51 附錄7 3-methyladenine (3-MA)抑制自噬作用 52 | |
| dc.language.iso | zh-TW | |
| dc.subject | ubiquitin | zh_TW |
| dc.subject | HDAC6 | zh_TW |
| dc.subject | 細胞膜修補 | zh_TW |
| dc.subject | 自噬作用 | zh_TW |
| dc.subject | ubiquitin | en |
| dc.subject | membrane repair | en |
| dc.subject | HDAC6 | en |
| dc.subject | autophagy | en |
| dc.title | 細胞膜修補誘發與HDAC6無關的自噬作用與
蛋白質聚集體形成 | zh_TW |
| dc.title | Membrane repair induced HDAC6-independent autophagy and aggresome formation | en |
| dc.type | Thesis | |
| dc.date.schoolyear | 97-2 | |
| dc.description.degree | 碩士 | |
| dc.contributor.oralexamcommittee | 黃銓珍(Chang-Jen Huang),李明亭(Ming-Ting Lee),陳宏文(Hung-wen Chen),張茂山(Mau-Sun Chang) | |
| dc.subject.keyword | 自噬作用,細胞膜修補,HDAC6,ubiquitin, | zh_TW |
| dc.subject.keyword | autophagy,membrane repair,HDAC6,ubiquitin, | en |
| dc.relation.page | 52 | |
| dc.rights.note | 有償授權 | |
| dc.date.accepted | 2009-07-28 | |
| dc.contributor.author-college | 生命科學院 | zh_TW |
| dc.contributor.author-dept | 生化科學研究所 | zh_TW |
| 顯示於系所單位： | 生化科學研究所 | |
文件中的檔案：
| 檔案 | 大小 | 格式 | |
|---|---|---|---|
| ntu-98-1.pdf 未授權公開取用 | 5.52 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。