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完整後設資料紀錄
DC 欄位 | 值 | 語言 |
---|---|---|
dc.contributor.advisor | 楊維元 | |
dc.contributor.author | Pei-Jou Liu | en |
dc.contributor.author | 劉珮柔 | zh_TW |
dc.date.accessioned | 2021-06-17T03:10:49Z | - |
dc.date.available | 2020-08-24 | |
dc.date.copyright | 2018-08-24 | |
dc.date.issued | 2018 | |
dc.date.submitted | 2018-07-18 | |
dc.identifier.citation | 1. I. Tzameli, The evolving role of mitochondria in metabolism. Trends in endocrinology and metabolism: TEM 23, 417-419 (2012).
2. L. Galluzzi, O. Kepp, C. Trojel-Hansen, G. Kroemer, Mitochondrial control of cellular life, stress, and death. Circulation research 111, 1198-1207 (2012). 3. K. Surendran, S. P. Vitiello, D. A. Pearce, Lysosome dysfunction in the pathogenesis of kidney diseases. Pediatric nephrology (Berlin, Germany) 29, 2253-2261 (2014). 4. D. M. Raiser, A. Narla, B. L. Ebert, The emerging importance of ribosomal dysfunction in the pathogenesis of hematologic disorders. Leukemia & lymphoma 55, 491-500 (2014). 5. D. C. Chan, Mitochondria: dynamic organelles in disease, aging, and development. Cell 125, 1241-1252 (2006). 6. C. C. Hsu, L. M. Tseng, H. C. Lee, Role of mitochondrial dysfunction in cancer progression. Experimental biology and medicine (Maywood, N.J.) 241, 1281-1295 (2016). 7. Y. Ohsumi, N. Mizushima, Two ubiquitin-like conjugation systems essential for autophagy. Seminars in cell & developmental biology 15, 231-236 (2004). 8. T. Inobe, A. Matouschek, Paradigms of protein degradation by the proteasome. Current opinion in structural biology 24, 156-164 (2014). 9. K. R. Parzych, D. J. Klionsky, An overview of autophagy: morphology, mechanism, and regulation. Antioxidants & redox signaling 20, 460-473 (2014). 10. J. Zhao et al., FoxO3 coordinately activates protein degradation by the autophagic/lysosomal and proteasomal pathways in atrophying muscle cells. Cell metabolism 6, 472-483 (2007). 11. Z. Lipatova, N. Segev, A Role for Macro-ER-Phagy in ER Quality Control. PLoS genetics 11, e1005390 (2015). 12. L. Murrow, J. Debnath, Autophagy as a stress-response and quality-control mechanism: implications for cell injury and human disease. Annual review of pathology 8, 105-137 (2013). 13. A. Ruggiano, O. Foresti, P. Carvalho, Quality control: ER-associated degradation: protein quality control and beyond. The Journal of cell biology 204, 869-879 (2014). 14. G. Kroemer, Autophagy: a druggable process that is deregulated in aging and human disease. The Journal of clinical investigation 125, 1-4 (2015). 15. Z. Deng et al., Autophagy Receptors and Neurodegenerative Diseases. Trends in cell biology 27, 491-504 (2017). 16. J. M. Zarzynska, The importance of autophagy regulation in breast cancer development and treatment. BioMed research international 2014, 710345 (2014). 17. T. Martins-Marques, T. Ribeiro-Rodrigues, P. Pereira, P. Codogno, H. Girao, Autophagy and ubiquitination in cardiovascular diseases. DNA and cell biology 34, 243-251 (2015). 18. Y. Feng, D. He, Z. Yao, D. J. Klionsky, The machinery of macroautophagy. Cell research 24, 24-41 (2014). 19. W. W. Li, J. Li, J. K. Bao, Microautophagy: lesser-known self-eating. Cellular and molecular life sciences : CMLS 69, 1125-1136 (2012). 20. S. Kaushik, A. M. Cuervo, Chaperone-mediated autophagy: a unique way to enter the lysosome world. Trends in cell biology 22, 407-417 (2012). 21. L. Galluzzi et al., Molecular definitions of autophagy and related processes. The EMBO journal 36, 1811-1836 (2017). 22. V. Rogov, V. Dotsch, T. Johansen, V. Kirkin, Interactions between autophagy receptors and ubiquitin-like proteins form the molecular basis for selective autophagy. Molecular cell 53, 167-178 (2014). 23. S. Shaid, C. H. Brandts, H. Serve, I. Dikic, Ubiquitination and selective autophagy. Cell death and differentiation 20, 21-30 (2013). 24. K. Okamoto, Organellophagy: eliminating cellular building blocks via selective autophagy. The Journal of cell biology 205, 435-445 (2014). 25. L. Liu, K. Sakakibara, Q. Chen, K. Okamoto, Receptor-mediated mitophagy in yeast and mammalian systems. Cell research 24, 787-795 (2014). 26. J. Hasegawa, I. Maejima, R. Iwamoto, T. Yoshimori, Selective autophagy: lysophagy. Methods (San Diego, Calif.) 75, 128-132 (2015). 27. L. D. Osellame, M. R. Duchen, Quality control gone wrong: mitochondria, lysosomal storage disorders and neurodegeneration. British journal of pharmacology 171, 1958-1972 (2014). 28. X. Cheng, X. Zhang, L. Yu, H. Xu, Calcium signaling in membrane repair. Seminars in cell & developmental biology 45, 24-31 (2015). 29. R. Bashir et al., A gene related to Caenorhabditis elegans spermatogenesis factor fer-1 is mutated in limb-girdle muscular dystrophy type 2B. Nature genetics 20, 37-42 (1998). 30. C. Tam et al., Exocytosis of acid sphingomyelinase by wounded cells promotes endocytosis and plasma membrane repair. The Journal of cell biology 189, 1027-1038 (2010). 31. J. Liu et al., Dysferlin, a novel skeletal muscle gene, is mutated in Miyoshi myopathy and limb girdle muscular dystrophy. Nature genetics 20, 31-36 (1998). 32. M. Corrotte, T. Castro-Gomes, A. B. Koushik, N. W. Andrews, Approaches for plasma membrane wounding and assessment of lysosome-mediated repair responses. Methods in cell biology 126, 139-158 (2015). 33. F. Grinnell, Fibroblast-collagen-matrix contraction: growth-factor signalling and mechanical loading. Trends in cell biology 10, 362-365 (2000). 34. P. L. McNeil, E. Warder, Glass beads load macromolecules into living cells. Journal of cell science 88 ( Pt 5), 669-678 (1987). 35. H. Wolfmeier et al., Ca(2)(+)-dependent repair of pneumolysin pores: A new paradigm for host cellular defense against bacterial pore-forming toxins. Biochimica et biophysica acta 1853, 2045-2054 (2015). 36. E. B. Babiychuk, K. Monastyrskaya, S. Potez, A. Draeger, Intracellular Ca(2+) operates a switch between repair and lysis of streptolysin O-perforated cells. Cell death and differentiation 16, 1126-1134 (2009). 37. Y. Sano, W. Watanabe, S. Matsunaga, Chromophore-assisted laser inactivation--towards a spatiotemporal-functional analysis of proteins, and the ablation of chromatin, organelle and cell function. Journal of cell science 127, 1621-1629 (2014). 38. K. Berg et al., Photochemical internalization: a novel technology for delivery of macromolecules into cytosol. Cancer research 59, 1180-1183 (1999). 39. N. Mehraban, H. S. Freeman, Developments in PDT Sensitizers for Increased Selectivity and Singlet Oxygen Production. Materials 8, 4421-4456 (2015). 40. J. P. Kamat, T. P. Devasagayam, K. I. Priyadarsini, H. Mohan, Reactive oxygen species mediated membrane damage induced by fullerene derivatives and its possible biological implications. Toxicology 155, 55-61 (2000). 41. P. L. McNeil, S. S. Vogel, K. Miyake, M. Terasaki, Patching plasma membrane disruptions with cytoplasmic membrane. Journal of cell science 113 ( Pt 11), 1891-1902 (2000). 42. V. Idone et al., Repair of injured plasma membrane by rapid Ca2+-dependent endocytosis. The Journal of cell biology 180, 905-914 (2008). 43. A. J. Jimenez et al., ESCRT machinery is required for plasma membrane repair. Science (New York, N.Y.) 343, 1247136 (2014). 44. C. Wasmeier, A. N. Hume, G. Bolasco, M. C. Seabra, Melanosomes at a glance. Journal of cell science 121, 3995-3999 (2008). 45. G. Raposo, D. Tenza, D. M. Murphy, J. F. Berson, M. S. Marks, Distinct protein sorting and localization to premelanosomes, melanosomes, and lysosomes in pigmented melanocytic cells. The Journal of cell biology 152, 809-824 (2001). 46. A. C. Theos, S. T. Truschel, G. Raposo, M. S. Marks, The Silver locus product Pmel17/gp100/Silv/ME20: controversial in name and in function. Pigment cell research 18, 322-336 (2005). 47. G. Raposo, M. S. Marks, Melanosomes – dark organelles enlighten endosomal membrane transport. Nature reviews. Molecular cell biology 8, 786-797 (2007). 48. I. Hurbain et al., Electron tomography of early melanosomes: implications for melanogenesis and the generation of fibrillar amyloid sheets. Proceedings of the National Academy of Sciences of the United States of America 105, 19726-19731 (2008). 49. V. J. Hearing, Biogenesis of pigment granules: a sensitive way to regulate melanocyte function. Journal of dermatological science 37, 3-14 (2005). 50. J. J. Bultema et al., Myosin vc interacts with Rab32 and Rab38 proteins and works in the biogenesis and secretion of melanosomes. The Journal of biological chemistry 289, 33513-33528 (2014). 51. N. Ohbayashi, M. Fukuda, Role of Rab family GTPases and their effectors in melanosomal logistics. Journal of biochemistry 151, 343-351 (2012). 52. E. M. Wolf Horrell, M. C. Boulanger, J. A. D’Orazio, Melanocortin 1 Receptor: Structure, Function, and Regulation. Frontiers in Genetics 7, 95 (2016). 53. D. Ploper, E. M. De Robertis, The MITF family of transcription factors: Role in endolysosomal biogenesis, Wnt signaling, and oncogenesis. Pharmacological research 99, 36-43 (2015). 54. M. L. Hartman, M. Czyz, MITF in melanoma: mechanisms behind its expression and activity. Cellular and molecular life sciences : CMLS 72, 1249-1260 (2015). 55. W. J. Yi et al., Degraded melanocores are incompetent to protect epidermal keratinocytes against UV damage. Cell cycle (Georgetown, Tex.), 1-40 (2018). 56. Z. Yang, B. Zeng, Y. Pan, P. Huang, C. Wang, Autophagy participates in isoliquiritigenin-induced melanin degradation in human epidermal keratinocytes through PI3K/AKT/mTOR signaling. Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie 97, 248-254 (2018). 57. L. Chen et al., Light-emitting diode 585nm photomodulation inhibiting melanin synthesis and inducing autophagy in human melanocytes Journal of dermatological science 89, 11-18 (2018). 58. Y. H. Hung, L. M. Chen, J. Y. Yang, W. Y. Yang, Spatiotemporally controlled induction of autophagy-mediated lysosome turnover. Nature communications 4, 2111 (2013). 59. C. W. Hsieh, C. H. Chu, H. M. Lee, W. Yuan Yang, Triggering mitophagy with far-red fluorescent photosensitizers. Scientific reports 5, 10376 (2015). 60. J. Y. Yang, W. Y. Yang, Spatiotemporally controlled initiation of Parkin-mediated mitophagy within single cells. Autophagy 7, 1230-1238 (2011). 61. J. Moan, A. Dahlback, R. B. Setlow, Epidemiological support for an hypothesis for melanoma induction indicating a role for UVA radiation. Photochemistry and photobiology 70, 243-247 (1999). 62. D. N. Peles, J. D. Simon, UV-absorption spectra of melanosomes containing varying 5,6-dihydroxyindole and 5,6-dihydroxyindole-2-carboxylic acid content. The journal of physical chemistry. B 115, 12624-12631 (2011). 63. D. N. Peles, J. D. Simon, The UV-absorption spectrum of human iridal melanosomes: a new perspective on the relative absorption of eumelanin and pheomelanin and its consequences. Photochemistry and photobiology 88, 1378-1384 (2012). 64. L. M. Baltazar et al., Melanin protects Paracoccidioides brasiliensis from the effects of antimicrobial photodynamic inhibition and antifungal drugs. Antimicrobial agents and chemotherapy 59, 4003-4011 (2015). 65. W. Korytowski, T. Sarna, Bleaching of melanin pigments. Role of copper ions and hydrogen peroxide in autooxidation and photooxidation of synthetic dopa-melanin. The Journal of biological chemistry 265, 12410-12416 (1990). 66. P. Ghosh, D. Ghosh, Elucidating the Photoprotection Mechanism of Eumelanin Monomers. The journal of physical chemistry. B 121, 5988-5994 (2017). 67. S. Ito et al., Roles of reactive oxygen species in UVA-induced oxidation of 5,6-dihydroxyindole-2-carboxylic acid-melanin as studied by differential spectrophotometric method. Pigment cell & melanoma research 29, 340-351 (2016). 68. A. Ramkumar et al., Classical autophagy proteins LC3B and ATG4B facilitate melanosome movement on cytoskeletal tracks. Autophagy 13, 1331-1347 (2017). 69. J. K. Jaiswal et al., S100A11 is required for efficient plasma membrane repair and survival of invasive cancer cells. Nature communications 5, 3795 (2014). | |
dc.identifier.uri | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/69220 | - |
dc.description.abstract | 胞器的品質控制對於生物的生存非常重要,過去眾多的文獻揭露許多疾病的發生與胞器品質控制失衡有關。受損的胞器一般皆經由細胞自噬作用(autophagy)清除,細胞自噬是細胞內自我分解機制的一種,而在過去不同的研究當中,也都證實細胞自噬參與在胞器的品質控制中。
於此,我們使用光誘導策略對C2C12肌肉纖維母細胞(C2C12 myoblast cell)的細胞膜,以及MNT-1黑色素細胞(MNT-1 melanocytes)和B16F1黑色素細胞 (B16F1 melanocytes)的黑色素體(melanosome)進行破壞。利用光敏劑(photosensitizer)的吸光特性,使用雷射光激發光敏劑產生活性氧化物(ROS),進而誘導細胞自噬作用進行。在雷射共軛焦顯微鏡下運用此方法,我們可以控制在單一細胞中,欲產生損傷的位置與損傷程度。 在本篇研究中,我們觀察到,在細胞膜受損後,細胞會立即進行修復,修復的模式可以大致區分為兩類:胞吞作用(endocytosis)與脫除作用(shedding)。根據損傷程度的不同,細胞會傾向啟動不同的作用機制,在細胞膜受損嚴重時,脫除作用的發生比率會提高,而在較輕微的損傷狀況下,則以胞吞作用為主。但不論受損程度之強弱,在受損細胞膜附近都能觀察到細胞膜的內噬(internalization),並且會被泛素(ubiquitin)標記,進而進行細胞自噬而被降解。而在受損黑色素體的研究中,我們發現可見光的中間波段可以用來誘導黑色素體的損傷,並且這些受損黑色素體會被泛素標記。而這樣被泛素化的現象,表示受損的黑色素體有可能會藉由細胞自噬作用來清除。 概括而言,我們使用光敏劑搭配光誘導策略對細胞膜和黑色素體進行破壞,利用此方法,可以控制對單一細胞欲產生損傷的位置與損傷程度。在細胞膜受損時,細胞會因著損傷程度的不同而有不同的修復策略,然而不論在何種損傷程度下,部分的膜會被內噬並進一步被泛素標定而進行細胞自噬降解。在誘導黑色素體損傷的部分,我們提供了一個更加簡便與精準的方法,可以幫助我們更深入去探討黑色素體的品質控制。 | zh_TW |
dc.description.abstract | Quality control of organelles is crucial for survival and numerous studies have revealed the relationship between organelles dysregulation and diseases. Damaged organelles are believed to be degraded through autophagy, and different research have proved the involvement of autophagy which is a “self-eating” degradative machinery in cell.
Here, we applied the light-induced scheme to impair plasma membrane of C2C12 myoblast cells, and the melanosomes in MNT-1 and B16F1 melanocytes. With the photosensitizer-based methodology, the photosensitizers were bleached to induce autophagy in the selective region. By combining the scheme with confocal microscope, we can spatiotemporally control the position and the severity in a single cell. In our observation, after the plasma membranes injury, cell would immediately undergo membrane repair through endocytosis and shedding. Depending on the severity, cells tended to conduct shedding at the strong damaged condition and favored endocytosis at the weak damaged condition. No matter how severe the damage, the internalization of damaged membrane usually happened, and the internalized membranes were targeted by ubiquitin to execute autophagy. As for melanosome, the middle of the visible spectrum could properly trigger the damage with ubiquitin targeting. And the ubiquitin recruitment indicated that the damaged melanosome may process autophagy for degradation. In summary, we utilized the photosensitizer-based impairment to spatiotemporally induce damaged plasma membrane and melanosome. In our observation, cells can choose their plasma membrane quality control procedure through sensing the severity of the injuries, and autophagy participates in the elimination of internalized membranes. The induction of damaged melanosome provides a precise and convenient methodology to discover the mechanism of melanosome quality control. | en |
dc.description.provenance | Made available in DSpace on 2021-06-17T03:10:49Z (GMT). No. of bitstreams: 1 ntu-107-R05B46009-1.pdf: 2185330 bytes, checksum: a53715e503829ca714282864d9715135 (MD5) Previous issue date: 2018 | en |
dc.description.tableofcontents | 致謝 i
摘要 ii Abstract iv Abbreviation vi CHAPTER 1. Introduction 1 Organelle quality control 1 Autophagy 1 Selective autophagy 2 Organellophagy 3 Plasma membrane 3 Methodologies in membrane injury induction 4 Cellular responses for damaged plasma membrane 4 Melanosome 5 UVR and LED illumination 6 CHAPTER 2. Material and Method 8 Material 8 Equipment 11 Methods 12 Cell culture 12 Plasmids 12 Transfection (Lipofectamine 2000) 12 Transfection (Viromer RED) 13 Co-transfection (Lipofectamine 2000) 14 Live-cell manipulation and imaging 14 Cell membrane staining with AlPcS2a and AF594-WGA 15 Tracking PI uptake 16 Selectively induction of plasma membrane damage without perturbing lysosome 16 Induction of membranes shedding 17 Detection of makers for selective autophagy: Ub and LC3 18 Detection of makers for selective autophagy: adaptor proteins 18 Immunofluorescence 18 UV irradiation induction of melanosome damage test 19 Visible light induction of melanosome damage test 19 CHAPTER 3. Result 21 Induction of specific photosensitizer-based plasma membrane injury 21 Cellular responses to damaged plasma membrane 23 Photosensitizer-based melanosome injury and cellular response to damaged melanosome 26 CHAPTER 4. Discussion 28 Specific photosensitizer-based plasma membrane injury 28 Membrane repair to damaged plasma membrane 28 Selective autophagy in the removal of damaged plasma membranes 29 Specific photosensitizer-based melanosome injury 30 Melanosome lighten after photobleaching 30 MNT-1 melanoma cells and B16F1 melanoma cells 31 Summary 32 Future works 33 CHAPTER 5. Figures 34 CHAPTER 6. References 46 CHAPTER 7. Appendix 56 | |
dc.language.iso | en | |
dc.title | 利用雷射光分別誘導細胞膜與黑色素體之損傷 | zh_TW |
dc.title | Triggering plasma membrane or melanosome damage by light | en |
dc.type | Thesis | |
dc.date.schoolyear | 106-2 | |
dc.description.degree | 碩士 | |
dc.contributor.oralexamcommittee | 陳光超,陳正繹 | |
dc.subject.keyword | 細胞自噬,泛素,細胞膜,黑色素體,CALI, | zh_TW |
dc.subject.keyword | autophagy,ubiquitin,plasma membrane,melanosome,CALI, | en |
dc.relation.page | 60 | |
dc.identifier.doi | 10.6342/NTU201801623 | |
dc.rights.note | 有償授權 | |
dc.date.accepted | 2018-07-18 | |
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 |
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