請用此 Handle URI 來引用此文件：
http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/46142完整後設資料紀錄
| DC 欄位 | 值 | 語言 |
|---|---|---|
| dc.contributor.advisor | 孟子青(Tzu-Ching Meng) | |
| dc.contributor.author | Yun-Chung Liu | en |
| dc.contributor.author | 劉昀宗 | zh_TW |
| dc.date.accessioned | 2021-06-15T04:55:23Z | - |
| dc.date.available | 2014-09-19 | |
| dc.date.copyright | 2011-09-19 | |
| dc.date.issued | 2011 | |
| dc.date.submitted | 2011-08-17 | |
| dc.identifier.citation | 參考文獻
1. Llinas, R., I. Z. Steinberg, et al. (1981). 'Relationship between Presynaptic Calcium Current and Postsynaptic Potential in Squid Giant Synapse.' Biophysical Journal 33(3): 323-351. 2. Connors, B. W. and M. A. Long (2004). 'Electrical synapses in the mammalian brain.' Annu Rev Neurosci 27: 393-418. 3. Wong, C. K. C., H. Y. Yeung, et al. (2002). 'Effects of dibutyryl cAMP on stanniocalcin and stanniocalcin-related protein mRNA expression in neuroblastoma cells.' Journal of Endocrinology 173(1): 199-209. 4. Richter-Landsberg, C. and B. Jastorff (1986). 'The role of cAMP in nerve growth factor-promoted neurite outgrowth in PC12 cells.' J Cell Biol 102(3): 821-829. 5. Daniels, R. H., P. S. Hall, et al. (1998). 'Membrane targeting of p21-activated kinase 1 (PAK1) induces neurite outgrowth from PC12 cells.' EMBO J 17(3): 754-764. 6. Ma'ayan, A., S. L. Jenkins, et al. (2009). 'Neuro2A differentiation by Galphai/o pathway.' Sci Signal 2(54): cm1. 7. Huang, E. J. and L. F. Reichardt (2003). 'Trk receptors: roles in neuronal signal transduction.' Annu Rev Biochem 72: 609-642. 8. Segal, R. A. and M. E. Greenberg (1996). 'Intracellular signaling pathways activated by neurotrophic factors.' Annu Rev Neurosci 19: 463-489. 9. Smith, S. J. (1988). 'Neuronal cytomechanics: the actin-based motility of growth cones.' Science 242(4879): 708-715. 10. Le Clainche, C. and M. F. Carlier (2008). 'Regulation of actin assembly associated with protrusion and adhesion in cell migration.' Physiol Rev 88(2): 489-513. 11. Schnapp, B. J., T. S. Reese, et al. (1992). 'Kinesin is bound with high affinity to squid axon organelles that move to the plus-end of microtubules.' J Cell Biol 119(2): 389-399. 12. Schnapp, B. J. and T. S. Reese (1989). 'Dynein is the motor for retrograde axonal transport of organelles.' Proc Natl Acad Sci U S A 86(5): 1548-1552. 13. Dent, E. W. and F. B. Gertler (2003). 'Cytoskeletal dynamics and transport in growth cone motility and axon guidance.' Neuron 40(2): 209-227. 14. Gissen, P. and E. R. Maher (2007). 'Cargos and genes: insights into vesicular transport from inherited human disease.' J Med Genet 44(9): 545-555. 15. Dahlstom, A., P. O. Heiwall, et al. (1975). 'Comparison between the effect of colchicine and lumicolchicine on axonal transport in rat motor neurons.' J Neural Transm 37(4): 305-311. 16. Avila, J., J. Dominguez, et al. (1994). 'Regulation of microtubule dynamics by microtubule-associated protein expression and phosphorylation during neuronal development.' Int J Dev Biol 38(1): 13-25. 17. Cravchik, A., D. Reddy, et al. (1994). 'Identification of a novel microtubule-binding domain in microtubule-associated protein 1A (MAP1A).' J Cell Sci 107 ( Pt 3): 661-672. 18. Hirokawa, N., T. Funakoshi, et al. (1996). 'Selective stabilization of tau in axons and microtubule-associated protein 2C in cell bodies and dendrites contributes to polarized localization of cytoskeletal proteins in mature neurons.' J Cell Biol 132(4): 667-679. 19. Littauer, U. Z., D. Giveon, et al. (1986). 'Common and distinct tubulin binding sites for microtubule-associated proteins.' Proc Natl Acad Sci U S A 83(19): 7162-7166. 20. Garner, C. C., R. P. Tucker, et al. (1988). 'Selective localization of messenger RNA for cytoskeletal protein MAP2 in dendrites.' Nature 336(6200): 674-677. 21. Litman, P., J. Barg, et al. (1993). 'Subcellular localization of tau mRNA in differentiating neuronal cell culture: implications for neuronal polarity.' Neuron 10(4): 627-638. 22. Okabe, S. and N. Hirokawa (1989). 'Rapid turnover of microtubule-associated protein MAP2 in the axon revealed by microinjection of biotinylated MAP2 into cultured neurons.' Proc Natl Acad Sci U S A 86(11): 4127-4131. 23. Kanai, Y. and N. Hirokawa (1995). 'Sorting mechanisms of tau and MAP2 in neurons: suppressed axonal transit of MAP2 and locally regulated microtubule binding.' Neuron 14(2): 421-432. 24. Liu, F. and C. X. Gong (2008). 'Tau exon 10 alternative splicing and tauopathies.' Mol Neurodegener 3: 8. 25. Martin, L., X. Latypova, et al. (2011). 'Post-translational modifications of tau protein: implications for Alzheimer's disease.' Neurochem Int 58(4): 458-471. 26. Cho, J. H. and G. V. Johnson (2004). 'Primed phosphorylation of tau at Thr231 by glycogen synthase kinase 3beta (GSK3beta) plays a critical role in regulating tau's ability to bind and stabilize microtubules.' J Neurochem 88(2): 349-358. 27. Biernat, J., N. Gustke, et al. (1993). 'Phosphorylation of Ser262 strongly reduces binding of tau to microtubules: distinction between PHF-like immunoreactivity and microtubule binding.' Neuron 11(1): 153-163. 28. Hanger, D. P. and S. Wray (2010). 'Tau cleavage and tau aggregation in neurodegenerative disease.' Biochem Soc Trans 38(4): 1016-1020. 29. Reifert, J., D. Hartung-Cranston, et al. (2011). 'Amyloid {beta}-Mediated Cell Death of Cultured Hippocampal Neurons Reveals Extensive Tau Fragmentation without Increased Full-length Tau Phosphorylation.' J Biol Chem 286(23): 20797-20811. 30. Sisodia, S. S. and D. L. Price (1995). 'Role of the beta-amyloid protein in Alzheimer's disease.' FASEB J 9(5): 366-370. 31. Zhang, X. and W. Le (2010). 'Pathological role of hypoxia in Alzheimer's disease.' Exp Neurol 223(2): 299-303. 32. Li, Q. Y., H. M. Wang, et al. (2010). 'Salidroside attenuates hypoxia-induced abnormal processing of amyloid precursor protein by decreasing BACE1 expression in SH-SY5Y cells.' Neurosci Lett 481(3): 154-158. 33. Fang, H., L. F. Zhang, et al. (2010). 'Acute hypoxia promote the phosphorylation of tau via ERK pathway.' Neurosci Lett 474(3): 173-177. 34. Wen, Y., S. Yang, et al. (2004). 'Transient cerebral ischemia induces site-specific hyperphosphorylation of tau protein.' Brain Res 1022(1-2): 30-38. 35. Morioka, M., T. Kawano, et al. (2006). 'Hyperphosphorylation at serine 199/202 of tau factor in the gerbil hippocampus after transient forebrain ischemia.' Biochem Biophys Res Commun 347(1): 273-278. 36. Rissman, R. A., W. W. Poon, et al. (2004). 'Caspase-cleavage of tau is an early event in Alzheimer disease tangle pathology.' J Clin Invest 114(1): 121-130. 37. Johnson, G. V. and W. H. Stoothoff (2004). 'Tau phosphorylation in neuronal cell function and dysfunction.' J Cell Sci 117(Pt 24): 5721-5729. 38. Garg, S., T. Timm, et al. (2011). 'Cleavage of Tau by calpain in Alzheimer's disease: the quest for the toxic 17 kD fragment.' Neurobiol Aging 32(1): 1-14. 39. Reifert, J., D. Hartung-Cranston, et al. (2011). 'Amyloid {beta}-Mediated Cell Death of Cultured Hippocampal Neurons Reveals Extensive Tau Fragmentation without Increased Full-length Tau Phosphorylation.' J Biol Chem 286(23): 20797-20811. 40. Choi, Y. E., M. Butterworth, et al. (2009). 'The E3 ubiquitin ligase cIAP1 binds and ubiquitinates caspase-3 and -7 via unique mechanisms at distinct steps in their processing.' J Biol Chem 284(19): 12772-12782. 41. Mannick, J. B. (2007). 'Regulation of apoptosis by protein S-nitrosylation.' Amino Acids 32(4): 523-526. 42. Ye, X., W. S. Kim, et al. (2007). 'Ubiquitous presence of argininosuccinate at millimolar levels in the central nervous system of Aplysia californica.' J Neurochem 101(3): 632-640. 43. Santolini, J. (2011). 'The molecular mechanism of mammalian NO-synthases: a story of electrons and protons.' J Inorg Biochem 105(2): 127-141. 44. Rand, M. J. and C. G. Li (1995). 'Nitric oxide as a neurotransmitter in peripheral nerves: nature of transmitter and mechanism of transmission.' Annu Rev Physiol 57: 659-682. 45. Khan, M., B. Sekhon, et al. (2005). 'S-Nitrosoglutathione reduces inflammation and protects brain against focal cerebral ischemia in a rat model of experimental stroke.' J Cereb Blood Flow Metab 25(2): 177-192. 46. Gidday, J. M., A. R. Shah, et al. (1999). 'Nitric oxide mediates cerebral ischemic tolerance in a neonatal rat model of hypoxic preconditioning.' J Cereb Blood Flow Metab 19(3): 331-340. 47. Bizzoco, E., M. G. Vannucchi, et al. (2007). 'Transient ischemia increases neuronal nitric oxide synthase, argininosuccinate synthetase and argininosuccinate lyase co-expression in rat striatal neurons.' Exp Neurol 204(1): 252-259. 48. Pignataro, G., A. Scorziello, et al. (2009). 'Post-ischemic brain damage: effect of ischemic preconditioning and postconditioning and identification of potential candidates for stroke therapy.' FEBS J 276(1): 46-57. 49. Castillo, J., R. Rama, et al. (2000). 'Nitric oxide-related brain damage in acute ischemic stroke.' Stroke 31(4): 852-857. 50. Iadecola, C. (1997). 'Bright and dark sides of nitric oxide in ischemic brain injury.' Trends Neurosci 20(3): 132-139. 51. Bartlett, W. P. and G. A. Banker (1984). 'An electron microscopic study of the development of axons and dendrites by hippocampal neurons in culture. I. Cells which develop without intercellular contacts.' J Neurosci 4(8): 1944-1953. 52. Banker, G. A. and W. M. Cowan (1977). 'Rat hippocampal neurons in dispersed cell culture.' Brain Res 126(3): 397-342. 53. Nakagawa, S., M. A. Deli, et al. (2009). 'A new blood-brain barrier model using primary rat brain endothelial cells, pericytes and astrocytes.' Neurochem Int 54(3-4): 253-263. 54. Bowman, P. D., A. L. Betz, et al. (1981). 'Primary culture of capillary endothelium from rat brain.' In Vitro 17(4): 353-362. 55. Perriere, N., P. Demeuse, et al. (2005). 'Puromycin-based purification of rat brain capillary endothelial cell cultures. Effect on the expression of blood-brain barrier-specific properties.' J Neurochem 93(2): 279-289. 56. Sun, Y., N. H. Kim, et al. (2011). 'Lysophosphatidic acid induces neurite retraction in differentiated neuroblastoma cells via GSK-3beta activation.' Mol Cells 31(5): 483-489. 57. Toriyama, M., Y. Sakumura, et al. (2010). 'A diffusion-based neurite length-sensing mechanism involved in neuronal symmetry breaking.' Mol Syst Biol 6: 394. 58. Arimura, N. and K. Kaibuchi (2007). 'Neuronal polarity: from extracellular signals to intracellular mechanisms.' Nat Rev Neurosci 8(3): 194-205. 59. Gamblin, T. C., F. Chen, et al. (2003). 'Caspase cleavage of tau: linking amyloid and neurofibrillary tangles in Alzheimer's disease.' Proc Natl Acad Sci U S A 100(17): 10032-10037. 60. Ethell, D. W., E. Bossy-Wetzel, et al. (2001). 'Caspase 7 can cleave tumor necrosis factor receptor-I (p60) at a non-consensus motif, in vitro.' Biochim Biophys Acta 1541(3): 231-238. 61. Loscalzo, J. and G. Welch (1995). 'Nitric oxide and its role in the cardiovascular system.' Prog Cardiovasc Dis 38(2): 87-104. 62. Gao, Y. and J. Usha Raj(2010). 'Hypoxic Pulmonary Hypertension of the Newborn.' Compr Physiol 1: 61-79. 63. Min, J., Y. M. Jin, et al. (2006). 'Hypoxia-induced endothelial NO synthase gene transcriptional activation is mediated through the tax-responsive element in endothelial cells.' Hypertension 47(6): 1189-1196. 64. Lakshmi, V. M. and T. V. Zenser (2007). '2-(4-Carboxyphenyl)-4,4,5,5-tetramethylimidazoline-1-oxyl-3-oxide potentiates nitrosation of a heterocyclic amine carcinogen by nitric oxide.' Life Sci 80(7): 644-649. 65. Low, S. Y. and K. R. Bruckdorfer (2004). 'Nitric oxide signaling in platelets.' Methods Mol Biol 273: 313-334. 66. Wolf, B. B., J. C. Goldstein, et al. (1999). 'Calpain functions in a caspase-independent manner to promote apoptosis-like events during platelet activation.' Blood 94(5): 1683-1692. 67. Fifre, A., I. Sponne, et al. (2006). 'Microtubule-associated protein MAP1A, MAP1B, and MAP2 proteolysis during soluble amyloid beta-peptide-induced neuronal apoptosis. Synergistic involvement of calpain and caspase-3.' J Biol Chem 281(1): 229-240. 68. Zhang, Z. G., M. Chopp, et al. (1993). 'Cerebral endothelial nitric oxide synthase expression after focal cerebral ischemia in rats.' Stroke 24(12): 2016-2021; discussion 2021-2012. 69. Malinski, T., F. Bailey, et al. (1993). 'Nitric oxide measured by a porphyrinic microsensor in rat brain after transient middle cerebral artery occlusion.' J Cereb Blood Flow Metab 13(3): 355-358. 70. Yu, C. X., S. Li, et al. (2005). 'Redox regulation of PTEN by S-nitrosothiols.' Mol Pharmacol 68(3): 847-854. 71. Frerart, F., I. Lobysheva, et al. (2009). 'Vascular caveolin deficiency supports the angiogenic effects of nitrite, a major end product of nitric oxide metabolism in tumors.' Mol Cancer Res 7(7): 1056-1063. | |
| dc.identifier.uri | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/46142 | - |
| dc.description.abstract | 摘要
神經細胞於大腦功能扮演重要角色，神經細胞軸突(Axon)可以傳遞訊息，控制生物行為。神經訊息傳導受阻於病理情況導致腦部功能嚴重喪失。中風，腦部疾病之一，是全世界致死疾病前三名，其中缺氧型中風(Ischemic stroke)是中風的主要類型。缺氧型中風經由血管阻塞使腦部缺氧，並引起腦部傷害。缺氧型中風對腦部造成傷害和引起行為活動失常，但是目前並不清楚基本的機制。Tau蛋白大量表現於軸突中，且可穩定細胞骨架中微管(Microtubule)結構，因此我們推測Tau蛋白於缺氧環境下失去其功能。本篇論文主旨是針對神經細胞Tau蛋白調控於缺氧環境扮演的角色功能探討。 我們於缺氧環境中觀察分化神經細胞Neuro-2a的神經纖維出現嚴重的縮減情形並伴隨著微管結構的崩解。此外我們也觀察到有趣的現象，缺氧刺激內生性的硫胱胺酸蛋白-3(Caspase-3)活化。而硫胱胺酸蛋白酶基質之一，Tau蛋白可能經由缺氧活化硫胱胺酸蛋白-3進行切割調控並失去穩固微管結構的功能。我們將以皮層神經細胞(Cortical neuron)進一步探討此假說。如同Neuro-2a，皮層神經細胞也經由缺氧引起神經纖維的縮減與微管崩解。我們將大量表現Tau蛋白的神經纖維認定為類軸突，並經缺氧處理造成此結構長度縮減。於類軸突結構我們可以觀察到Tau蛋白與微管結構的關聯性。我們得到重要的結果，當皮層神經細胞加入硫胱胺酸蛋白酶抑制劑Z-DEVD抑制硫胱胺酸蛋白酶，可以防止缺氧引起的Tau瓦解、微管崩解與神經纖維縮減。因此我們假設一氧化氮(Nitric oxide, NO)可以防止硫胱胺酸蛋白酶的活性。無論是Neuro-2a還是皮質神經細胞加入S-亞硝基半胱胺酸(S-nitrosocysteine, CSNO)於缺氧環境的確有效保持微管與軸突結構的完整性。此外我們利用共同培養皮層神經細胞與內皮細胞也證實一氧化氮的功效，內皮細胞釋放一氧化氮保護皮層神經細胞的軸突與神經纖維。於此處我們提出經由一氧化氮保持神經功能的新奇機制。 | zh_TW |
| dc.description.abstract | Abstract
Neurons play an important role in brain function and transport signals through axon to control behavior. Pathological conditions that impair signal transduction of neurons lead to severe dysfunction of brain. Among such conditions, stroke is the third cause of death worldwide. Ischemic stroke is the major type of stroke and the brain damage is caused by blocking blood flow and result in low level of oxygen supply to tissue. Ischemic stroke-induced brain damage and motor dysfunction may result from neuron death and axon injury. However, the underlying mechanism remains elusive. We proposed that Tau, which is highly enriched in axon and stabilizes microtubule, may lose its function under low-oxygen conditions. Therefore, in this study we have focused on the regulatory role of Tau under hypoxia in cultured neuronal cells. When well-differentiated Neuro-2a (N2a) cells were cultured in hypoxia condition, we observed that neurites were undergoing significant retraction in conjugation with microtubule collapse. Interestingly, endogenous expression of Caspase-3 in N2a cells was activated in response to hypoxia, suggesting that Tau, which has been shown as a substrate of caspases, might be cleaved thus losing its protective role in maintenance of microtubule integrity. We tested this hypothesis in primary rat cortical neurons. Consistently, hypoxia insults in cortical neurons led to neurite retraction and microtubule collapse. The Tau-enriched neurite, which was regarded as an axon-like structure, also underwent profound shortening during the course of hypoxic treatment. Focusing on this axon-like structure, we observed that Tau was regarded in association with fragmentation of microtubule. Importantly, when caspases were inactivated by a specific inhibitor, hypoxia-induced degradation of Tau, fragmentation of microtubule and retraction of axon were prevented in cortical neurons. We then hypothesized that nitric oxide (NO) might inactivate caspase, thus exerting a protective role. Indeed, exposure of N2a cells and cortical neurons to S-nitrosocysteine (CSNO) resulted in significant preservation of microtubule integrity and axon structure against hypoxic insults. The protective effect of NO was illustrated by co-culturing cortical neurons together with endothelia under hypoxia. We showed that NO released from endothelia prevented axons and neurites of cortical neurons from hypoxia-mediated disruption. Taken together, we propose a novel NO-dependent mechanism for protecting neuronal functions, against hypoxia-induced insult. | en |
| dc.description.provenance | Made available in DSpace on 2021-06-15T04:55:23Z (GMT). No. of bitstreams: 1 ntu-100-R98b46021-1.pdf: 75871822 bytes, checksum: f4c9d1c2df2558cc5203bf973899d455 (MD5) Previous issue date: 2011 | en |
| dc.description.tableofcontents | 目錄
口試委員會審定書--------------------------------------------------------------------------------------i 誌謝--------------------------------------------------------------------------------------------------------ii 中文摘要-------------------------------------------------------------------------------------------------iii 英文摘要-------------------------------------------------------------------------------------------------iv 目錄--------------------------------------------------------------------------------------------------------vi 緒論---------------------------------------------------------------------------------------------------------1 神經訊息傳遞-------------------------------------------------------------------------------------1 環磷酸腺苷(3'-5'-cyclic adenosine monophosphate, cAMP)與神經生長因子(Nerve Growth Factor, NGF)刺激神經纖維增生(Neurite outgrowth)-----------------------------2 神經細胞細胞骨架(Cytoskeleton)-------------------------------------------------------------2 微管相關蛋白(Microtubule associated protein, MAP)--------------------------------------3 硫胱胺酸蛋白脢-3、7(Caspase3、7)---------------------------------------------------------5 一氧化氮(nitric oxide, NO)----------------------------------------------------------------------5 實驗方法--------------------------------------------------------------------------------------------------7 一、細胞培養---------------------------------------------------------------------------------------7 二、刺激Neuro-2a神經纖維增生(Neurite outgrowth)--------------------------------------8 三、正常含氧量(Normoxia)與缺氧(Hypoxia)環境設定-----------------------------------9 四、測量神經纖維長度(Neurite length)與統計分析---------------------------------------9 五、免疫螢光染色(Immunofluorescence)----------------------------------------------------10 六、蛋白質萃取----------------------------------------------------------------------------------10 七、蛋白質濃度測定----------------------------------------------------------------------------11 八、西方墨點法(Western blot)-----------------------------------------------------------------12 九、一氧化氮施體(NO donor)與硫胱胺酸蛋白脢抑制劑(Caspase inhibitor)處理-13 十、轉染(Transfection)---------------------------------------------------------------------------14 十一、硫胱胺酸蛋白酶-3活性偵測(Caspase 3 activity assay)--------------------------14 十二、細胞共同培養系統(Co-culture system)----------------------------------------------14 實驗材料-------------------------------------------------------------------------------------------------15 實驗結果-------------------------------------------------------------------------------------------------19 一、環磷酸腺苷(3'-5'-cyclic adenosine monophosphate, cAMP)可促進神經細胞Neuro-2a 分化，而神經生長因子(Nerve Growth Factor, NGF)並無顯著促進分化的能力---------------------------------------------------------------------------------------------19 二、Hank平衡鹽溶液(Hank’s balanced salt solution, HBSS)提供合適的缺氧型中風模擬環境---------------------------------------------------------------------------------------20 三、細胞骨架(Cytoskeleton)崩解於缺氧環境可能與神經纖維縮減相關----------22 四、缺氧所活化的硫胱胺酸蛋白脢(Caspase)可能經由硫胱胺酸蛋白脢切割微管相關蛋白(Microtubule associated protein, MAP) Tau引起細胞骨架崩解------------23 五、一氧化氮(Nitric oxide, NO)有助於減緩神經細胞的缺氧傷害，並可能經由抑制硫胱胺酸蛋白脢的活性保持神經纖維的完整性---------------------------------25 六、皮層神經細胞(Cortical neuron)對於缺氧反應相似於神經細胞株Neuro-2a，亦產生缺氧引起之神經纖維縮減----------------------------------------------------------26 七、缺氧引起的皮層神經細胞微管相關蛋白分布與微管崩解有時間順序上的關聯-------------------------------------------------------------------------------------------------27 八、大量表現Tau蛋白於皮質神經細胞可以增加對抗缺氧的容忍度，維持較完整的微管結構---------------------------------------------------------------------------------29 九、大腦皮層神經細胞經由硫胱胺酸蛋白脢調控缺氧造成的軸突縮減、微管崩解與微管相關蛋白瓦解--------------------------------------------------------------------30 十、一氧化氮增加大腦皮層神經細胞對於缺氧的容忍度，延緩缺氧造成的軸突縮減、微管崩解與微管相關蛋白瓦解--------------------------------------------------32 十一、硫胱胺酸蛋白脢於神經細胞上的分布--------------------------------------------33 十二、一氧化氮與Z-DEVD於缺氧環境抑制硫胱胺酸蛋白脢活性與Tau蛋白切割-------------------------------------------------------------------------------------------------34 十三、內皮細胞於缺氧環境釋放一氧化氮保護神經細胞----------------------------35 討論-------------------------------------------------------------------------------------------------------37 一、環磷酸腺苷(3'-5'-cyclic adenosine monophosphate, cAMP)與神經生長因子(Nerve Growth Factor, NGF)刺激神經纖維增生------------------------------------------37 二、Tau蛋白切割(Cleavage)調控與磷酸化(Phosphorylation)修飾--------------------38 三、缺氧情況活化硫胱胺酸蛋白酶(Caspase)並增加Tau切割修飾，非由鈣蛋白酶(Calpain)引起----------------------------------------------------------------------------------39 四、MAP2是否也於缺氧環境受到硫胱胺酸蛋白酶切割修飾-----------------------40 五、缺氧對微管(Microtubule)與微管相關蛋白(Microtubule associated protein, MAP)時間與空間的變化-----------------------------------------------------------------------------40 六、一氧化氮(Nitric oxide, NO)對於神經細胞的影響----------------------------------41 七、一氧化氮清除劑c-PTIO的作用--------------------------------------------------------42 後續實驗規劃------------------------------------------------------------------------------------------43 圖表-------------------------------------------------------------------------------------------------------44 Figure 1---------------------------------------------------------------------------------------------44 Figure 2---------------------------------------------------------------------------------------------46 Figure 3---------------------------------------------------------------------------------------------50 Figure 4---------------------------------------------------------------------------------------------52 Figure 5---------------------------------------------------------------------------------------------54 Figure 6---------------------------------------------------------------------------------------------55 Figure 7---------------------------------------------------------------------------------------------57 Figure 8---------------------------------------------------------------------------------------------59 Figure 9---------------------------------------------------------------------------------------------61 Figure 10-------------------------------------------------------------------------------------------65 Figure 11-------------------------------------------------------------------------------------------69 Figure 12-------------------------------------------------------------------------------------------71 Figure 13-------------------------------------------------------------------------------------------74 Figure 14-------------------------------------------------------------------------------------------76 Figure 15-------------------------------------------------------------------------------------------77 Figure 16-------------------------------------------------------------------------------------------80 Figure 17-------------------------------------------------------------------------------------------82 Figure 18-------------------------------------------------------------------------------------------83 Figure 19-------------------------------------------------------------------------------------------85 Figure 20-------------------------------------------------------------------------------------------87 Figure 21-------------------------------------------------------------------------------------------89 參考文獻-------------------------------------------------------------------------------------------------92 | |
| dc.language.iso | zh-TW | |
| dc.subject | Tau蛋白 | zh_TW |
| dc.subject | 缺氧 | zh_TW |
| dc.subject | 一氧化氮 | zh_TW |
| dc.subject | 硫胱胺酸蛋白-3 | zh_TW |
| dc.subject | 神經纖維 | zh_TW |
| dc.subject | 神經細胞 | zh_TW |
| dc.subject | 微管 | zh_TW |
| dc.subject | nitric oxide | en |
| dc.subject | neuron | en |
| dc.subject | microtubule | en |
| dc.subject | neurite | en |
| dc.subject | caspase-3 | en |
| dc.subject | Tau | en |
| dc.subject | hypoxia | en |
| dc.title | 探討一氧化氮於缺氧環境中對神經細胞的保護作用 | zh_TW |
| dc.title | NO-mediated Neuroprotection under Hypoxic Conditions | en |
| dc.type | Thesis | |
| dc.date.schoolyear | 99-2 | |
| dc.description.degree | 碩士 | |
| dc.contributor.oralexamcommittee | 林天南(Teng-nan Lin),鄭敬楓 | |
| dc.subject.keyword | 神經細胞,缺氧,微管,神經纖維,硫胱胺酸蛋白-3,Tau蛋白,一氧化氮, | zh_TW |
| dc.subject.keyword | neuron,hypoxia,microtubule,neurite,caspase-3,Tau,nitric oxide, | en |
| dc.relation.page | 96 | |
| dc.rights.note | 有償授權 | |
| dc.date.accepted | 2011-08-18 | |
| 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 | |
文件中的檔案：
| 檔案 | 大小 | 格式 | |
|---|---|---|---|
| ntu-100-1.pdf 未授權公開取用 | 74.09 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。