博碩士論文 93224004 詳細資訊



以作者查詢圖書館館藏 、以作者查詢臺灣博碩士 、以作者查詢全國書目 、勘誤回報 、線上人數：15 、訪客IP：3.148.108.201
姓名 劉芳君(Fang-Chun Liu)  查詢紙本館藏   畢業系所 生命科學系
論文名稱 亞砷酸鈉誘引有絲分裂期CGL-2細胞死亡機制之研究
(The mechanism of arsenite-induced mitotic death in CGL-2 cells)
相關論文
★ 三氯乙烯與四氯乙烯對人類肺癌細胞之毒性研究★ Galectin-1 與 Thioredoxin peroxidase II 基因之選殖及表現
★ 亞砷酸鈉誘引分裂中期停滯細胞之蛋白質體研究★ Galectin-1蛋白與亞砷酸鈉毒性與結合作用之研究
★ 氧化壓迫與p53參與三氯乙烯及四氯乙烯誘導人類肺癌細胞凋亡之研究★ Thioredoxin Peroxidase II蛋白與亞砷酸鈉毒性與結合作用之研究
★ 環型類★ 亞砷酸鈉與Galectin-1蛋白交互作用之研究
★ PAG蛋白質對三氧化二砷誘發急性前骨髓性白血癌細胞毒性之角色研究★ Galectin-1蛋白對細胞生長於幾丁聚醣膜上的影響及調控機制之研究
★ 低劑量亞砷酸鈉誘引第一型血紅素氧化酶調控路徑之研究★ 砷化物抑制Galectin-1基因之表現及機制之研究
★ 砷化物誘導Thioredoxin Peroxidase II蛋白之表現及機制之研究★ Galectin-1蛋白促進老鼠軟骨細胞於幾丁聚醣修飾之聚乳酸-聚乙酸醇共聚物支架生長之研究
★ Galectin-1對亞砷酸鈉毒性影響之研究★ Galectin-1誘導前脂肪細胞分化機制之研究
檔案 [Endnote RIS 格式]    [Bibtex 格式]    [相關文章]   [文章引用]   [完整記錄]   [館藏目錄]   [檢視]  [下載]
  1. 本電子論文使用權限為同意立即開放。
  2. 已達開放權限電子全文僅授權使用者為學術研究之目的，進行個人非營利性質之檢索、閱讀、列印。
  3. 請遵守中華民國著作權法之相關規定，切勿任意重製、散佈、改作、轉貼、播送，以免觸法。

摘要(中) 砷化物會造成許多腫瘤細胞進行不正常的有絲分裂，使細胞停滯在有絲分裂期，進而促使細胞走向細胞凋亡。本研究探討亞砷酸鈉造成CGL-2細胞停滯在有絲分裂期後進行細胞凋亡的機制。為了解亞砷酸鈉如何引起細胞停滯在有絲分裂期與啟動細胞凋亡，利用西方點墨法觀察有絲分裂管制點和細胞凋亡的蛋白質表現，結果顯示亞砷酸鈉在短時間內就會造成有絲分裂停滯，有絲分裂管制點活化，之後參與粒線體相關細胞凋亡的蛋白開始活化，並發生凋亡。將短時間與長時間停滯在分裂期的細胞做比較，發現透過粒線體產生的細胞凋亡在長時間的停滯後才明顯發生，並伴隨Bax構形改變、粒線體膜電位喪失與caspase活化；而自由基的產生在短時間停滯的細胞就被誘導，但卻沒有顯著的細胞凋亡的發生，且非分裂期的細胞並沒有明顯自由基的產生。這些結果說明，亞砷酸鈉造成細胞停滯在有絲分裂期後會誘導自由基產生，進而誘發粒線體相關的細胞凋亡。JNK和p38在亞砷酸鈉誘發的分裂期停滯及細胞凋亡的過程中被明顯磷酸化，顯示它們可能參與砷導致分裂期細胞凋亡的過程。另一方面，利用二維電泳發現STI1在亞砷酸鈉停滯在分裂期的細胞中有較高的表現量。除此之外，為了探討中心體倍增的機制，利用 g-tubulin做免疫沉澱，發現許多與 g-tubulin 結合的蛋白在亞砷酸鈉停滯在分裂期的細胞中表現較多，可能和砷引起的中心體倍增有關。本實驗證實亞砷酸鈉使細胞停滯在有絲分裂，造成有絲分裂管制點的活化，引發自由基的產生或累積，並可能透過JNK、p38、STI1和一些與中心體倍增相關的蛋白使長時間停滯在有絲分裂的細胞走向粒線體相關的細胞凋亡。
摘要(英) Arsenite can induce mitotic abnormalities, mitotic arrest, and subsequently lead to mitosis-mediated apoptosis in a variety of cancer cell lines. Knowledge of the mechanism of mitotic death can help realizing the toxicity of arsenite. In the present study, we confirmed the effects of arsenite on mitotic arrest and mitotic death in CGL-2 cells. To dissect how cell death was initiated in these mitotic arrested cells, the expression status of several mitotic checkpoint proteins and apoptotic proteins during arsenite-induced mitotic arrest were examined by Western blot analysis. The results showed that arsenite induced the activation of mitotic checkpoint. The apoptotic proteins were activated after protracted activation of the mitotic checkpoint. In addition, change of Bax conformation, loss of mitochondria membrane potential, and initiation of apoptosis was significantly induced in the long-term arsenite-arrested mitotic cells. Furthermore, ROS generation was noticed in short-term and long-term arsenite-arrested mitotic cells but not in interphase cells. These results indicated that ROS was generated after arsenite-induced mitotic arrest and mitochondria-mediated apoptosis was preceded with ROS generation. JNK and p38 were phosphorylated during arsenite-induced mitotic arrest and mitotic death indicating the activation of JNK and p38 might be involved in arsenite-induced mitotic arrest and mitotic death. On the other hand, 2D electrophoresis analysis revealed that the expression of stress-induced-phosphoprotein 1 (STI1) was higher in arsenite-arrested mitotic cells than in normal mitotic cells. Analysis of centrosome-associated proteins in normal or arsenite-arrested mitotic cells by immunoprecipitation with g-tubulin antibodies revealed that the expression of several proteins was higher in arsenite-arrested mitotic cells than in normal mitotic cells. These proteins might be involved in arsenite- induced centrosome amplification. Our results strongly suggested that inappropriate mitosis induced by arsenite could lead to the activation of mitotic checkpoint and the generation of ROS. The prolonged activation of mitotic checkpoint could lead to mitochondria-mediated apoptosis probably through JNK, p38, STI1, and some centrosome amplification-associated proteins.
關鍵字(中) ★ 砷
★ 有絲分裂		 關鍵字(英) ★ mitosis
★ arsenite
論文目次 摘要 i
Abstract ii
List of contents iv
List of figures vi
List of table vii
Chapter 1. Introduction 1
1. Introduction of arsenic compounds 1
1.1 Distribution and uses of arsenic in the environment 1
1.2 Effects of arsenic compounds on human health 2
1.3 The proposed mechanisms involved in arsenic toxicity 3
2. The effects of arsenic compound on cell cycle progression 5
2.1. An overview of the cell cycle 5
2.2. The centrosome 6
2.3. The cell cycle control system 7
2.4. The effects of arsenic on cell cycle progression 9
3. Induction of apoptosis and mitotic death 10
3.1. Apoptosis 11
3.2. Mitotic death 12
4. Objectives 14
Chapter 2. Materials and Methods 16
1. Cell culture 16
2. Preparation of normal mitotic cells 16
3. Arsenite treatment 16
4. Analysis of cell cycle progression and mitotic index 17
5. Apoptosis assay 18
6. Western blot analysis 18
7. Detection of Bax conformational change 19
8. Flow cytometric analysis of loss of mitochondria membrane potential 20
9. Analysis of ROS generation 20
9.1. Generation of superoxide anion (O2.-) 20
9.2. Generation of hydrogen peroxide (H2O2) 21
10. Two-dimensional gel electrophoresis and image analysis 21
11. γ-tubulin immunoprecipitation 22
12. In-gel enzymatic digestion and mass spectrometry 23
Chapter 3. Results 24
1. Induction of mitochondria-dependent apoptosis was associated with prolonged mitotic arrest and mitotic checkpoint activation induced by arsenite 24
1.1. Mitotic checkpoint was significantly and persistently activated in arsenite-arrested mitotic cells 24
1.2. Mitochondria-mediated apoptosis was induced after protracted activation of mitotic checkpoint 25
1.3. High level of apoptosis was induced in long-term arsenite- arrested mitotic cells 26
1.4. Change of Bax conformation and loss of MMP were induced in the long-term arsenite-arrested mitotic cells 28
2. The generation of ROS in arsenite-arrested mitotic cells 30
2.1. ROS was generated in short-term and long-term arsenite- arrested mitotic cells 30
2.2. JNK and p38 were phosphorylated during arsenite-induced mitotic arrest and mitotic death 31
3. Identification of the proteins differently expressed in normal and arsenite-arrested mitotic cells by 2D electrophoresis 32
4. Expression pattern of centrosome-associated protein in arsenite-arrested mitotic cells 33
Chapter 4. Discussion 34
1. Prolonged mitotic arrest and mitotic checkpoint activation was essential for arsenite-induced mitotic death 34
2. Roles of caspase 3 and phosphorylated Bcl-2, Bim, and Bad in mitosis and in arsenite-induced mitotic arrest 37
3. The generation of ROS in arsenite-arrested mitotic cells 40
4. The chaperone pathway might be involved in arsenite- induced mitotic arrest and mitotic death 41
5. The expression pattern of centrosome-associated proteins in normal and arsenite-arrested mitotic cells 42
Chapter 5. Conclusion 44
References 65
參考文獻 1. Kirk T. Kitchin, K. W. Dissociation of arsenite-peptide complexes: Triphasic nature, rate constants, half-lives, and biological importance. Journal of Biochemical and Molecular Toxicology 20, 48-56 (2006).
2. Antman, K. H. Introduction: The History of Arsenic Trioxide in Cancer Therapy. Oncologist 6, 1-2 (2001).
3. Roboz GJ, Dias S & al., L. G. e. Arsenic trioxide induces dose- and time-dependent apoptosis of endothelium and may exert an antileukemic effect via inhibition of angiogenesis. Blood 96, 1525-1530 (2000).
4. Kitchin, K. T. Recent Advances in Arsenic Carcinogenesis: Modes of Action, Animal Model Systems, and Methylated Arsenic Metabolites. Toxicology and Applied Pharmacology 172, 249-261 (2001).
5. Tseng, W. P. Effects and dose--response relationships of skin cancer and blackfoot disease with arsenic. Environ Health Perspect 19, 109-19 (1977).
6. Duker, A. A., Carranza, E. J. M. & Hale, M. Arsenic geochemistry and health. Environment International 31, 631-641 (2005).
7. Konkola, K. More than a coincidence? The arrival of arsenic and the disappearance of plague in early modern Europe. J. Hist Med Allied Sci 47, 186-209 (1992).
8. Waxman, S. & Anderson, K. C. History of the development of arsenic derivatives in cancer therapy. Oncologist 6 Suppl 2, 3-10 (2001).
9. Smith, A. H., Lingas, E. O. & Rahman, M. Contamination of drinking-water by arsenic in Bangladesh: A public health emergency. Bulletin of the World Health Organization 78, 1093-1103 (2000).
10. Niu, C. et al. Studies on Treatment of Acute Promyelocytic Leukemia With Arsenic Trioxide: Remission Induction, Follow-Up, and Molecular Monitoring in 11 Newly Diagnosed and 47 Relapsed Acute Promyelocytic Leukemia Patients. Blood 94, 3315-3324 (1999).
11. Zhu, J. et al. Arsenic-induced PML targeting onto nuclear bodies: Implications for the treatment of acute?romyelocytic?eukemia. PNAS 94, 3978-3983 (1997).
12. Melnick, A. & Licht, J. D. Deconstructing a Disease: RAR{alpha}, Its Fusion Partners, and Their Roles in the Pathogenesis of Acute Promyelocytic Leukemia. Blood 93, 3167-3215 (1999).
13. Soignet, S. L. et al. Complete Remission after Treatment of Acute Promyelocytic Leukemia with Arsenic Trioxide. N Engl J Med 339, 1341-1348 (1998).
14. Roboz, G. J. et al. Arsenic trioxide induces dose- and time-dependent apoptosis of endothelium and may exert an antileukemic effect via inhibition of angiogenesis. Blood 96, 1525-1530 (2000).
15. Rousselot, P. et al. Arsenic Trioxide and Melarsoprol Induce Apoptosis in Plasma Cell Lines and in Plasma Cells from Myeloma Patients. Cancer Res 59, 1041-1048 (1999).
16. Park, W. H. et al. Arsenic Trioxide-mediated Growth Inhibition in MC/CAR Myeloma Cells via Cell Cycle Arrest in Association with Induction of Cyclin-dependent Kinase Inhibitor, p21, and Apoptosis. Cancer Res 60, 3065-3071 (2000).
17. Wang, Z.-G. et al. Arsenic Trioxide and Melarsoprol Induce Programmed Cell Death in Myeloid Leukemia Cell Lines and Function in a PML and PML-RARalpha Independent Manner. Blood 92, 1497-1504 (1998).
18. Chen, G. Q. et al. In vitro studies on cellular and molecular mechanisms of arsenic trioxide (As2O3) in the treatment of acute promyelocytic leukemia: As2O3 induces NB4 cell apoptosis with downregulation of Bcl-2 expression and modulation of PML-RAR alpha/PML proteins. Blood 88, 1052-1061 (1996).
19. Jing, Y., Dai, J., Chalmers-Redman, R. M. E., Tatton, W. G. & Waxman, S. Arsenic Trioxide Selectively Induces Acute Promyelocytic Leukemia Cell Apoptosis Via a Hydrogen Peroxide-Dependent Pathway. Blood 94, 2102-2111 (1999).
20. Huang, X. J., Wiernik, P. H., Klein, R. S. & Gallagher, R. E. Arsenic trioxide induces apoptosis of myeloid leukemia cells by activation of caspases. Med Oncol 16, 58-64 (1999).
21. Qian, Y., Castranova, V. & Shi, X. New perspectives in arsenic-induced cell signal transduction. Journal of Inorganic Biochemistry 96, 271-278 (2003).
22. Cooper, G. M. The Cell - A Molecular Approach. 2nd ed. (Sinauer Associates, Inc, Sunderland (MA), 2000).
23. Alberts, B. et al. Molecular Biology of the Cell 4th ed. (Garland Publishing, New York, 2002).
24. Rieder, C. L., Faruki, S. & Khodjakov, A. The centrosome in vertebrates: more than a microtubule-organizing center. Trends in Cell Biology 11, 413-419 (2001).
25. Meraldi, P. & Nigg, E. A. The centrosome cycle. FEBS Letters 521, 9-13 (2002).
26. Nigg, E. A. Centrosome aberrations: cause or consequence of cancer progression? Nat Rev Cancer 2, 815-25 (2002).
27. Castedo, M., Perfettini, J. L., Roumier, T. & Kroemer, G. Cyclin-dependent kinase-1: linking apoptosis to cell cycle and mitotic catastrophe. Cell Death Differ 9, 1287-93 (2002).
28. Nigg, E. A. Mitotic kinases as regulators of cell division and its checkpoints. Nat Rev Mol Cell Biol 2, 21-32 (2001).
29. VA, S. & RH, M. Checking out the G2/M transition. Biochim. Biophys. Acta 1519, 1-12 (2001).
30. Melo J & D., T. A unified view of the DNA-damage checkpoint. Curr. Opin. Cell. Biol. 14, 237-245 (2002).
31. Weaver, B. A. & Cleveland, D. W. Decoding the links between mitosis, cancer, and chemotherapy: The mitotic checkpoint, adaptation, and cell death. Cancer Cell 8, 7-12 (2005).
32. Yu, H. Regulation of APC-Cdc20 by the spindle checkpoint. Current Opinion in Cell Biology 14, 706-714 (2002).
33. Wassmann, K. & Benezra, R. Mad2 transiently associates with an APC/p55Cdc complex during mitosis. PNAS 95, 11193-11198 (1998).
34. Li, Y., Gorbea, C., Mahaffey, D., Rechsteiner, M. & Benezra, R. MAD2 associates with the cyclosome/anaphase-promoting complex and inhibits its activity. Proc Natl Acad Sci U S A 94, 12431-6 (1997).
35. Shah, J. V. & Cleveland, D. W. Waiting for Anaphase: Mad2 and the Spindle Assembly Checkpoint. Cell 103, 997-1000 (2000).
36. Tang, Z., Bharadwaj, R., Li, B. & Yu, H. Mad2-Independent inhibition of APCCdc20 by the mitotic checkpoint protein BubR1. Dev Cell 1, 227-37 (2001).
37. Mao, Y., Abrieu, A. & Cleveland, D. W. Activating and Silencing the Mitotic Checkpoint through CENP-E-Dependent Activation/Inactivation of BubR1. Cell 114, 87-98 (2003).
38. Li, W. et al. BUBR1 Phosphorylation Is Regulated during Mitotic Checkpoint Activation. Cell Growth Differ 10, 769-775 (1999).
39. Masayuki Nitta et al. Spindle checkpoint function is required for mitotic catastrophe induced by DNA-damaging agents. Oncogene 23, 6548-6558 (2004).
40. Fang, G. Checkpoint Protein BubR1 Acts Synergistically with Mad2 to Inhibit Anaphase-promoting Complex. Mol. Biol. Cell 13, 755-766 (2002).
41. Bharadwaj, R. & Yu, H. The spindle checkpoint, aneuploidy, and cancer. Oncogene 23, 2016-27 (2004).
42. Hoyt, M. A. A new view of the spindle checkpoint. J. Cell Biol. 154, 909-912 (2001).
43. Katsuya Takenaka, Y. G., and Eisuke Nishida. MAP Kinase Is Required for the Spindle Assembly Checkpoint but Is Dispensable for the Normal M Phase Entry and Exit in Xenopus Egg Cell Cycle Extracts. The Journal of Cell Biology 36, 1091-1097 (1997).
44. Geley, S. et al. Anaphase-promoting Complex/Cyclosome-dependent Proteolysis of Human Cyclin A Starts at the Beginning of Mitosis and Is Not Subject to the Spindle Assembly Checkpoint. J. Cell Biol. 153, 137-148 (2001).
45. Gorbsky, G. J. The mitotic spindle checkpoint. Current Biology 11, R1001-R1004 (2001).
46. Kops, G. J., Weaver, B. A. & Cleveland, D. W. On the road to cancer: aneuploidy and the mitotic checkpoint. Nat Rev Cancer 5, 773-85 (2005).
47. Castedo, M. et al. Cell death by mitotic catastrophe: a molecular definition. Oncogene 23, 2825-37 (2004).
48. Wang, T. S., Kuo, C. F., Jan, K. Y. & Huang, H. Arsenite induces apoptosis in Chinese hamster ovary cells by generation of reactive oxygen species. Journal Of Cellular Physiology 169, 256-268 (1996).
49. Van Loo, G. et al. Endonuclease G: A mitochondrial protein released in apoptosis and involved in caspase-independent DNA degradation. Cell Death and Differentiation 8, 1136-1142 (2001).
50. Lynn, S., Gurr, J.-R., Lai, H.-T. & Jan, K.-Y. NADH Oxidase Activation Is Involved in Arsenite-Induced Oxidative DNA Damage in Human Vascular Smooth Muscle Cells. Circ Res 86, 514-519 (2000).
51. Wang, T.-S. et al. Arsenite induces oxidative DNA adducts and DNA-protein cross-links in mammalian cells. Free Radical Biology and Medicine 31, 321-330 (2001).
52. Hei, T. K., Liu, S. X. & Waldren, C. Mutagenicity of arsenic in mammalian cells: Role of reactive oxygen species. PNAS 95, 8103-8107 (1998).
53. Samikkannu, T. et al. Reactive Oxygen Species Are Involved in Arsenic Trioxide Inhibition of Pyruvate Dehydrogenase Activity. Chem. Res. Toxicol. 16, 409-414 (2003).
54. Vega, L., Gonsebatt,M.E. and Ostrosky-Wegman,P. Aneugenic effect of sodium arsenite on human lymphocytes in vitro: an individual susceptibility effect detected. Mutat. Res., 334, 365-373 (1995).
55. Lee, T. C., Wang-Wuu,S., Huang,R.Y., Lee,K.C. and Jan,K.Y. Differential effects of pre- and posttreatment of sodium arsenite on the genotoxicity of methyl methanesulfonate in Chinese hamster ovary cells. Cancer Res 46, 1854-1857 (1986).
56. Tinwell, H., Stephens,S.C. and Ashby,J. Arsenite as the probable active species in the human carcinogenicity of arsenic: mouse micronucleus assays on Na and K arsenite, orpiment, and Fowler's solution. Environ. Hlth Perspect. 95, 205-210 (1991).
57. Wang, T. S. a. H., H. Active oxygen species are involved in the induction of micronuclei by arsenite in XRS-5 cells. Mutagenesis 9, 253-257 (1994).
58. Yih, L. H., Ho,I.C. and Lee,T.C. Sodium arsenite disturbs mitosis and induces chromosome loss in human fibroblasts. Cancer Res. 57 (1997).
59. Lee, T. C., Oshimura,M. and Barrett,J.C. Comparison of arsenic-induced cell transformation, cytotoxicity, mutation and cytogenetic effects in Syrian hamster embryo cells in culture. Carcinogenesis 6, 1421-1426 (1985).
60. Lee, T. C., Tanaka,N., Lamb,P.W., Gilmer,T.M. and Barrett,J.C. Induction of gene amplification by arsenic. Science 241 (1988).
61. Chen, F. & Shi, X. Intracellular signal transduction of cells in response to carcinogenic metals. Critical Reviews in Oncology/Hematology 42, 105-121 (2002).
62. Zhang, W. et al. The induction of apoptosis and cell cycle arrest by arsenic trioxide in lymphoid neoplasms. Leukemia 12, 1383-91 (1998).
63. Ma, D. C. et al. Selective induction of apoptosis of NB4 cells from G2+M phase by sodium arsenite at lower doses. Eur J Haematol 61, 27-35 (1998).
64. Hyun Park, W. et al. Arsenic trioxide inhibits the growth of A498 renal cell carcinoma cells via cell cycle arrest or apoptosis. Biochemical and Biophysical Research Communications 300, 230-235 (2003).
65. Chen, F. et al. Opposite Effect of NF-kappa B and c-Jun N-terminal Kinase on p53-independent GADD45 Induction by Arsenite. J. Biol. Chem. 276, 11414-11419 (2001).
66. Yih, L.-H., Tseng, Y.-Y., Wu, Y.-C. & Lee, T.-C. Induction of Centrosome Amplification during Arsenite-Induced Mitotic Arrest in CGL-2 Cells. Cancer Res 66, 2098-2106 (2006).
67. Liu, Q., Hilsenbeck, S. & Gazitt, Y. Arsenic trioxide-induced apoptosis in myeloma cells: p53-dependent G1 or G2/M cell cycle arrest, activation of caspase-8 or caspase-9, and synergy with APO2/TRAIL. Blood 101, 4078-4087 (2003).
68. Yih, L.-H., Hsueh, S.-W., Luu, W.-S., Chiu, T. H. & Lee, T.-C. Arsenite induces prominent mitotic arrest via inhibition of G2 checkpoint activation in CGL-2 cells. Carcinogenesis 26, 53-63 (2005).
69. Okada, H. & Mak, T. W. Pathways of apoptotic and non-apoptotic death in tumour cells. Nat Rev Cancer 4, 592-603 (2004).
70. Jacobson, M. D., Weil, M. & Raff, M. C. Programmed Cell Death in Animal Development. Cell 88, 347-354 (1997).
71. Los, M., Stroh, C., Janicke, R. U., Engels, I. H. & Schulze-Osthoff, K. Caspases: more than just killers? Trends in Immunology 22, 31-34 (2001).
72. Budihardjo, I., Oliver, H., Lutter, M., Luo, X. & Wang, X. Biochemical pathways of caspase activation during apoptosis. Annu Rev Cell Dev Biol 15, 269-90 (1999).
73. Yoshihide, T. Cell death regulation by the Bcl-2 protein family in the mitochondria. Journal of Cellular Physiology 195, 158-167 (2003).
74. Martin, S. S. & Vuori, K. Regulation of Bcl-2 proteins during anoikis and amorphosis. Biochimica et Biophysica Acta (BBA) - Molecular Cell Research 1692, 145-157 (2004).
75. Green, D. R. & Reed, J. C. Mitochondria and apoptosis. Science 281, 1309-12 (1998).
76. Li, P. et al. Cytochrome c and dATP-dependent formation of Apaf-1/caspase-9 complex initiates an apoptotic protease cascade. Cell 91, 479-89 (1997).
77. Ayscough K, H. J., MacNeill SA, Nurse P. Cold-sensitive mutants of p34cdc2 that suppress a mitotic catastrophe phenotype in fission yeast. Mol Gen Genet. 232, 344-350 (1992).
78. Brown, J. M. & Attardi, L. D. The role of apoptosis in cancer development and treatment response. Nat Rev Cancer 5, 231-7 (2005).
79. Castedo, M. et al. The cell cycle checkpoint kinase Chk2 is a negative regulator of mitotic catastrophe. Oncogene 23, 4353-61 (2004).
80. Taylor, B. F. et al. P53 suppression of arsenite-induced mitotic catastrophe is mediated by p21CIP1/WAF1. J Pharmacol Exp Ther, jpet.106.103077 (2006).
81. Jordan, M. A. et al. Mitotic block induced in HeLa cells by low concentrations of paclitaxel (Taxol) results in abnormal mitotic exit and apoptotic cell death. Cancer Res 56, 816-25 (1996).
82. Carvalho, A., Carmena, M., Sambade, C., Earnshaw, W. C. & Wheatley, S. P. Survivin is required for stable checkpoint activation in taxol-treated HeLa cells. J Cell Sci 116, 2987-2998 (2003).
83. Lanni, J. S. & Jacks, T. Characterization of the p53-Dependent Postmitotic Checkpoint following Spindle Disruption. Mol. Cell. Biol. 18, 1055-1064 (1998).
84. Burns, T. F., Fei, P., Scata, K. A., Dicker, D. T. & El-Deiry, W. S. Silencing of the Novel p53 Target Gene Snk/Plk2 Leads to Mitotic Catastrophe in Paclitaxel (Taxol)-Exposed Cells. Mol. Cell. Biol. 23, 5556-5571 (2003).
85. Yih, L. H., Ho, I. C. & Lee, T. C. Sodium arsenite disturbs mitosis and induces chromosome loss in human fibroblasts. Cancer Research 57, 5051-5059 (1997).
86. Huang, S. C. & Lee, T. C. Arsenite inhibits mitotic division and perturbs spindle dynamics in HeLa S3 cells. Carcinogenesis 19, 889-896 (1998).
87. Stanbridge, E. J., Flandermeyer, R. R., Daniels, D. W. & Nelson-Rees, W. A. Specific chromosome loss associated with the expression of tumorigenicity in human cell hybrids. Somatic Cell Genet. 7, 699--712 (1981).
88. Stein, G. S. & Borun, T. W. The synthesis of acidic chromosomal proteins during the cell cycle of HeLa S-3 cells. I. The accelerated accumulation of acidic residual nuclear protein before the initiation of DNA replication. J. Cell Biol. 52, 292--307 (1972).
89. Doherty SC, M. S., McKelvey-Martin V, et al. Cell cycle checkpoint function in bladder cancer. J Natl Cancer Inst 95, 1859–68 (2003).
90. Laemmli, U. K. Cleavage of structural proteins during the assembly of the head of bacteriophage T4. Nature 227, 680--685 (1970).
91. Zheng, Y. et al. Arsenic trioxide (As2O3) induces apoptosis through activation of Bax in hematopoietic cells. Oncogene 24, 3339-3347 (2005).
92. Yamaguchi, H. et al. Epothilone B analogue (BMS-247550)-mediated cytotoxicity through induction of Bax conformational change in human breast cancer cells. Cancer Res 62, 466-71 (2002).
93. Hsu, Y.-T. & Youle, R. J. Nonionic Detergents Induce Dimerization among Members of the Bcl-2 Family. J. Biol. Chem. 272, 13829-13834 (1997).
94. Bradford, M. M. A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding. Anal. Biochem. 72, 248--254 (1976).
95. Cossarizza, A., M.Baccarani-Contri, G. Kalashnikova & Franceschi., C. A new method for the cytofluorimetric analysis of mitochondrial membrane potential using the J-aggregate forming lipophilic cation 5,5',6,6'- tetrachloro-1,1',3,3'-tetraethylbenzimidazolcarbocyanine iodide (JC-1). 197, 40-45 (1993).
96. Kasianowicz, J., Benz, R. & McLaughlin, S. The kinetic mechanism by which CCCP (carbonyl cyanide m-chlorophenylhydrazone) transports protons across membranes. J. Membr. Biol. 82, 179-190 (1984).
97. Lesca, C. et al. DNA damage induce [gamma]-tubulin-RAD51 nuclear complexes in mammalian cells. 24, 5165-5172 (2005).
98. Li, D. Q. et al. Identification of breast cancer metastasis-associated proteins in an isogenic tumor metastasis model using two-dimensional gel electrophoresis and liquid chromatography-ion trap-mass spectrometry. Proteomics 6, 3352-68 (2006).
99. Murray, A. Cell cycle checkpoints. Current Opinion in Cell Biology 6, 872-876 (1994).
100. Davidovic, L., Vodenicharov, M., Affar, E. B. & Poirier, G. G. Importance of poly(ADP-ribose) glycohydrolase in the control of poly(ADP-ribose) metabolism. Exp Cell Res 268, 7-13 (2001).
101. Chyan-Jang Lee, Ching-Len Liao & Lin, Y.-L. Flavivirus Activates Phosphatidylinositol 3-Kinase Signaling To Block Caspase-Dependent Apoptotic Cell Death at the Early Stage of Virus Infection. 79 13, 8388 (2005).
102. Hsu, S. L. et al. Caspase 3, periodically expressed and activated at G2/M transition, is required for nocodazole-induced mitotic checkpoint. Apoptosis (2006).
103. Cohen, G. M. Caspases: the executioners of apoptosis. Biochem. J. 326, 1-16 (1997).
104. Li, P., D. Nijhawan, I. Budihardjo, S. M. Srinivasula, M. Ahmad, E. S. Alnemri, and X. Wang. . Cytochrome c and dATP-dependent formation of Apaf-1/caspase-9 complex initiates an apoptotic protease cascade. Cell 91, 479-489 (1997).
105. Paquet, C., Schmitt, E., Beauchemin, M. & Bertrand, R. Activation of multidomain and BH3-only pro-apoptotic Bcl-2 family members in p53-defective cells. Apoptosis 9, 815-31 (2004).
106. Brichese, L., Barboule, N., Heliez, C. & Valette, A. Bcl-2 Phosphorylation and Proteasome-Dependent Degradation Induced by Paclitaxel Treatment: Consequences on Sensitivity of Isolated Mitochondria to Bid. Experimental Cell Research 278, 101-111 (2002).
107. Scorrano, L. et al. A Distinct Pathway Remodels Mitochondrial Cristae and Mobilizes Cytochrome c during Apoptosis. Developmental Cell 2, 55-67 (2002).
108. Yamaguchi, H. & Wang, H.-G. Bcl-XL Protects BimEL-induced Bax Conformational Change and Cytochrome c Release Independent of Interacting with Bax or BimEL. J. Biol. Chem. 277, 41604-41612 (2002).
109. Green and John, C., nbsp & Reed, D. R. Mitochondria and Apoptosis. Science 281, 1309-1312 (1998).
110. Roucou X., M. J. C. Conformational change of Bax: a question of life or death. Cell Death Differ 8, 875-877 (2001).
111. Marchetti, M. A., Weinberger, M., Murakami, Y., Burhans, W. C. & Huberman, J. A. Production of reactive oxygen species in response to replication stress and inappropriate mitosis in fission yeast. J Cell Sci 119, 124-131 (2006).
112. Torres, M., Forman, H. J. Redox signaling and the MAP kinase pathways. Biofactors 17, 287-296 (2003).
113. Wang, T. H., Wang, H. S. & Soong, Y. K. Paclitaxel-induced cell death: where the cell cycle and apoptosis come together. Cancer 88, 2619-28 (2000).
114. Shin, H. J. et al. Inhibition of histone deacetylase activity increases chromosomal instability by the aberrant regulation of mitotic checkpoint activation. Oncogene 22, 3853-8 (2003).
115. Takenaka, K., Gotoh, Y. & Nishida, E. MAP kinase is required for the spindle assembly checkpoint but is dispensable for the normal M phase entry and exit in Xenopus egg cell cycle extracts. J Cell Biol 136, 1091-7 (1997).
116. Henzel WJ, B. T., Stults JT, Wong SC, Grimley C, Watanabe C. Identifying proteins from two-dimensional gels by molecular mass searching of peptide fragments in protein sequence databases. Proc Natl Acad Sci USA 90, 5011-5015 (1993).
117. Song, Y. & Masison, D. C. Independent Regulation of Hsp70 and Hsp90 Chaperones by Hsp70/Hsp90-organizing Protein Sti1 (Hop1). J. Biol. Chem. 280, 34178-34185 (2005).
118. Tao, W. et al. Induction of apoptosis by an inhibitor of the mitotic kinesin KSP requires both activation of the spindle assembly checkpoint and mitotic slippage. Cancer Cell 8, 49-59 (2005).
119. Dewson, G., Snowden, R. T., Almond, J. B., Dyer, M. J. & Cohen, G. M. Conformational change and mitochondrial translocation of Bax accompany proteasome inhibitor-induced apoptosis of chronic lymphocytic leukemic cells. Oncogene 22, 2643-54 (2003).
120. Roninson, I. B., Broude, E. V. & Chang, B.-D. If not apoptosis, then what? Treatment-induced senescence and mitotic catastrophe in tumor cells. Drug Resistance Updates 4, 303-313 (2001).
121. Bunz, F. et al. Requirement for p53 and p21 to Sustain G2 Arrest After DNA Damage. Science 282, 1497-1501 (1998).
122. Chan, T. A., Hermeking, H., Lengauer, C., Kinzler, K. W. & Vogelstein, B. 14-3-3[sigma] is required to prevent mitotic catastrophe after DNA damage. Nature 401, 616-620 (1999).
123. Cogswell, J. P., Brown, C. E., Bisi, J. E. & Neill, S. D. Dominant-Negative Polo-like Kinase 1 Induces Mitotic Catastrophe Independent of cdc25C Function. Cell Growth Differ 11, 615-623 (2000).
124. Huang, S.-C., Huang, C.-Y. F. & Lee, T.-C. Induction of mitosis-mediated apoptosis by sodium arsenite in HeLa S3 cells. Biochemical Pharmacology 60, 771-780 (2000).
125. Whitfield, M. L. et al. Identification of genes periodically expressed in the human cell cycle and their expression in tumors. Mol Biol Cell 13, 1977-2000 (2002).
126. Kim, M. et al. Caspase-Mediated Specific Cleavage of BubR1 Is a Determinant of Mitotic Progression. Mol. Cell. Biol. 25, 9232-9248 (2005).
127. C. Paquet, E. S., M. Beauchemin and R. Bertrand. Activation of multidomain and BH3-only pro-apoptotic Bcl-2 family members in p53-defective cells. Apoptosis 9, 815-831 (2004).
128. Furukawa, Y. et al. Phosphorylation of Bcl-2 Protein by CDC2 Kinase during G2/M Phases and Its Role in Cell Cycle Regulation. J. Biol. Chem. 275, 21661-21667 (2000).
129. Yamamoto, K. I., Hidenori; Korsmeyer, Stanley J. BCL-2 is phosphorylated and inactivated by an ASK1/Jun N-terminal protein kinase pathway normally activated at G2/M. Molecular and Cellular Biology 19, 8469-8478 (1999).
130. Lund, T., Stokke, T., Olsen, O. E. & Fodstad, O. Garlic arrests MDA-MB-435 cancer cells in mitosis, phosphorylates the proapoptotic BH3-only protein BimEL and induces apoptosis. Br J Cancer 92, 1773-81 (2005).
131. Lei K & RJ., D. JNK phosphorylation of Bim-related members of the Bcl-2 family induces Bax-dependent apoptosis. Proc Natl Acad Sci USA 100, 2432-2437 (2003).
132. Luciano F et al. Phosphorylation of BimEL by ERK1/2 on serine 69 promotes its degradation via the proteasome pathway and regulates its proapoptotic function. Oncogene 22, 6785-6793 (2003).
133. Mário Grãos, A. D. A., and Sukalyan Chatterjee. Growth-factor-dependent phosphorylation of Bim in mitosis. Biochemical Journal 388, 185-194 (2005).
134. Putcha GV, L. S., Frank S, Besirli CG, Clark K, Chu B, Alix S, Youle RJ, LaMarche A, Maroney AC, Johnson EM. . JNK-mediated Bim phosphorylation potentiates BAX-dependent apoptosis. Neuron 38, 899-914 (2003).
135. Cheng, E. H. et al. BCL-2, BCL-X(L) sequester BH3 domain-only molecules preventing BAX- and BAK-mediated mitochondrial apoptosis. Mol Cell 8, 705-11 (2001).
136. Konishi, Y., Lehtinen, M., Donovan, N. & Bonni, A. Cdc2 phosphorylation of BAD links the cell cycle to the cell death machinery. Mol Cell 9, 1005-16 (2002).
137. Berndtsson, M. et al. Phosphorylation of BAD at Ser-128 during mitosis and paclitaxel-induced apoptosis. FEBS Letters 579, 3090-3094 (2005).
138. Blagosklonny MV, G. P., el-Deiry WS, Kingston DG, Higgs PI, Neckers L, Fojo T. Raf-1/bcl-2 phosphorylation: a step from microtubule damage to cell death. Cancer Res 57, 130-135 (1997).
139. Srivastava RK, S. A., Korsmeyer SJ, Nesterova M, Cho-Chung YS, Longo DL. Involvement of microtubules in the regulation of Bcl2 phosphorylation and apoptosis through cyclic AMP-dependent protein kinase. Mol Cell Biol. 18, 3509-3517 (1998).
140. Pathan N, A.-S. C., Kitada S, Basu A, Haldar S, Reed JC. Microtubule-targeting drugs induce bcl-2 phosphorylation and association with Pin1. Neoplasia. 3, 550-559 (2001).
141. Calastretti A, B. A., Ceriani C, Vigano S, Zancai P, Capaccioli S, Nicolin A. Damaged microtubules can inactivate BCL-2 by means of the mTOR kinase. Oncogene 20, 6172-6180 (2001).
142. Gosslau A, R. L. Oxidativer Stress, altersabha¨ngige Zellscha¨digungen und antioxidative Mechanismen (Oxidative stress, age-related cell damage and antioxidative mechanisms). Z Gerontol Geriatr 35 (2002).
143. Fleury C, M. B., Vayssiere JL. Mitochondrial reactive oxygen species in cell death signaling. Biochimie 84, 131-141 (2002).
144. Reed, J. C. Apoptosis-targeted therapies for cancer. Cancer Cell 3, 17-22 (2003).
145. Takeda K, M. A., Nishitoh H, Ichijo H. Roles of MAPKKK ASK1 in stress-induced cell death. Cell struct Funct. 28, 23-29 (2003).
146. Picard, D. Heat-shock protein 90, a chaperone for folding and regulation. Cellular and Molecular Life Sciences 59, 1640-1648 (2002).
147. Prodromou, C. et al. Regulation of Hsp90 ATPase activity by tetratricopeptide repeat (TPR)-domain co-chaperones. EMBO Journal 18, 754-762 (1999).
148. Hernandez, M. P., Chadli, A. & Toft, D. O. HSP40 Binding Is the First Step in the HSP90 Chaperoning Pathway for the Progesterone Receptor. J. Biol. Chem. 277, 11873-11881 (2002).
149. Chen, S., Prapapanich, V., Rimerman, R. A., Honore, B. & Smith, D. F. Interactions of p60, a mediator of progesterone receptor assembly, with heat shock proteins hsp90 and hsp70. Mol Endocrinol 10, 682-93 (1996).
150. Wegele, H., Wandinger, S. K., Schmid, A. B., Reinstein, J. & Buchner, J. Substrate Transfer from the Chaperone Hsp70 to Hsp90. Journal of Molecular Biology 356, 802-811 (2006).
151. Wegele, H., Haslbeck, M., Reinstein, J. & Buchner, J. Sti1 is a novel activator of the Ssa proteins. Journal of Biological Chemistry 278, 25970-25976 (2003).
152. Ochi, T., Suzuki, T., Barrett, J. C. & Tsutsui, T. A trivalent dimethylarsenic compound, dimethy
larsine iodide, induces cellular transformation, aneuploidy, centrosome abnormality and multipolar spindle formation in Syrian hamster embryo cells. Toxicology 203, 155-163 (2004).
153. Kellog, D. R., Moritz, M. & Albert, B. M. The centrosome and cellular organization. Ann. Rev. Biochem 63, 639-674 (1994).
154. Sato, N., Mizumoto, K., Nakamura, M. & Tanaka, M. Radiation-Induced Centrosome Overduplication and Multiple Mitotic Spindles in Human Tumor Cells. Experimental Cell Research 255, 321-326 (2000).
155. Hsu, Y.-T. & Youle, R. J. Bax in Murine Thymus Is a Soluble Monomeric Protein That Displays Differential Detergent-induced Conformations. J. Biol. Chem. 273, 10777-10783 (1998).
指導教授 黃榮南、易玲輝
(Rong-Nan Huang、Ling-Huei Yih) 		審核日期 2006-7-7
推文 facebook   plurk   twitter   funp   google   live   udn   HD   myshare   reddit   netvibes   friend   youpush   delicious   baidu   
網路書籤 Google bookmarks   del.icio.us   hemidemi   myshare   

若有論文相關問題，請聯絡國立中央大學圖書館推廣服務組 TEL:(03)422-7151轉57407，或E-mail聯絡  - 隱私權政策聲明