請用此 Handle URI 來引用此文件:
http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/58276
完整後設資料紀錄
DC 欄位 | 值 | 語言 |
---|---|---|
dc.contributor.advisor | 張明富 | |
dc.contributor.author | Yi-Chen Kuo | en |
dc.contributor.author | 郭逸楨 | zh_TW |
dc.date.accessioned | 2021-06-16T08:10:03Z | - |
dc.date.available | 2017-10-09 | |
dc.date.copyright | 2014-10-09 | |
dc.date.issued | 2014 | |
dc.date.submitted | 2014-04-08 | |
dc.identifier.citation | 1. Accili, D. 2004. Lilly lecture 2003: the struggle for mastery in insulin action: from triumvirate to republic. Diabetes 53:1633-1642.
2. Akimoto, T., B. S. Sorg, and Z. Yan. 2004. Real-time imaging of peroxisome proliferator-activated receptor-gamma coactivator-1alpha promoter activity in skeletal muscles of living mice. American journal of physiology. Cell physiology 287:C790-796. 3. Altarejos, J. Y., and M. Montminy. 2011. CREB and the CRTC co-activators: sensors for hormonal and metabolic signals. Nature reviews. Molecular cell biology 12:141-151. 4. Aly, H. H., K. Watashi, M. Hijikata, H. Kaneko, Y. Takada, H. Egawa, S. Uemoto, and K. Shimotohno. 2007. Serum-derived hepatitis C virus infectivity in interferon regulatory factor-7-suppressed human primary hepatocytes. Journal of hepatology 46:26-36. 5. Banerjee, S., K. Saito, M. Ait-Goughoulte, K. Meyer, R. B. Ray, and R. Ray. 2008. Hepatitis C virus core protein upregulates serine phosphorylation of insulin receptor substrate-1 and impairs the downstream akt/protein kinase B signaling pathway for insulin resistance. Journal of virology 82:2606-2612. 6. Bartenschlager, R., L. Ahlborn-Laake, J. Mous, and H. Jacobsen. 1994. Kinetic and structural analyses of hepatitis C virus polyprotein processing. Journal of virology 68:5045-5055. 7. Bartenschlager, R., V. Lohmann, and F. Penin. 2013. The molecular and structural basis of advanced antiviral therapy for hepatitis C virus infection. Nature reviews. Microbiology 11:482-496. 8. Basaranoglu, M., and G. Basaranoglu. 2011. Pathophysiology of insulin resistance and steatosis in patients with chronic viral hepatitis. World journal of gastroenterology : WJG 17:4055-4062. 9. Behrens, S. E., L. Tomei, and R. De Francesco. 1996. Identification and properties of the RNA-dependent RNA polymerase of hepatitis C virus. The EMBO journal 15:12-22. 10. Benga, W. J., S. E. Krieger, M. Dimitrova, M. B. Zeisel, M. Parnot, J. Lupberger, E. Hildt, G. Luo, J. McLauchlan, T. F. Baumert, and C. Schuster. 2010. Apolipoprotein E interacts with hepatitis C virus nonstructural protein 5A and determines assembly of infectious particles. Hepatology 51:43-53. 11. Bernsmeier, C., F. H. Duong, V. Christen, P. Pugnale, F. Negro, L. Terracciano, and M. H. Heim. 2008. Virus-induced over-expression of protein phosphatase 2A inhibits insulin signalling in chronic hepatitis C. Journal of hepatology 49:429-440. 12. Bernsmeier, C., and M. H. Heim. 2009. Insulin resistance in chronic hepatitis C: mechanisms and clinical relevance. Swiss medical weekly 139:678-684. 13. Brown, E. A., H. Zhang, L. H. Ping, and S. M. Lemon. 1992. Secondary structure of the 5' nontranslated regions of hepatitis C virus and pestivirus genomic RNAs. Nucleic acids research 20:5041-5045. 14. Bugianesi, E., A. J. McCullough, and G. Marchesini. 2005. Insulin resistance: a metabolic pathway to chronic liver disease. Hepatology 42:987-1000. 15. Bukh, J., R. H. Purcell, and R. H. Miller. 1992. Sequence analysis of the 5' noncoding region of hepatitis C virus. Proceedings of the National Academy of Sciences of the United States of America 89:4942-4946. 16. Bukh, J., R. H. Purcell, and R. H. Miller. 1994. Sequence analysis of the core gene of 14 hepatitis C virus genotypes. Proceedings of the National Academy of Sciences of the United States of America 91:8239-8243. 17. Cha, T. A., E. Beall, B. Irvine, J. Kolberg, D. Chien, G. Kuo, and M. S. Urdea. 1992. At least five related, but distinct, hepatitis C viral genotypes exist. Proceedings of the National Academy of Sciences of the United States of America 89:7144-7148. 18. Chen, P. J., M. H. Lin, K. F. Tai, P. C. Liu, C. J. Lin, and D. S. Chen. 1992. The Taiwanese hepatitis C virus genome: sequence determination and mapping the 5' termini of viral genomic and antigenomic RNA. Virology 188:102-113. 19. Chen, S. L., and T. R. Morgan. 2006. The natural history of hepatitis C virus (HCV) infection. International journal of medical sciences 3:47-52. 20. Chen, Y. C., W. C. Su, J. Y. Huang, T. C. Chao, K. S. Jeng, K. Machida, and M. M. Lai. 2010. Polo-like kinase 1 is involved in hepatitis C virus replication by hyperphosphorylating NS5A. Journal of virology 84:7983-7993. 21. Choo, Q. L., K. H. Richman, J. H. Han, K. Berger, C. Lee, C. Dong, C. Gallegos, D. Coit, R. Medina-Selby, P. J. Barr, A. J. Weiner, D. W. Bradley, G. Kuo, and M. Houghton. 1991. Genetic organization and diversity of the hepatitis C virus. Proceedings of the National Academy of Sciences of the United States of America 88:2451-2455. 22. Christen, V., S. Treves, F. H. Duong, and M. H. Heim. 2007. Activation of endoplasmic reticulum stress response by hepatitis viruses up-regulates protein phosphatase 2A. Hepatology 46:558-565. 23. Cuenda, A., and S. Rousseau. 2007. p38 MAP-kinases pathway regulation, function and role in human diseases. Biochimica et biophysica acta 1773:1358-1375. 24. Daitoku, H., J. Sakamaki, and A. Fukamizu. 2011. Regulation of FoxO transcription factors by acetylation and protein-protein interactions. Biochimica et biophysica acta 1813:1954-1960. 25. Deak, M., A. D. Clifton, L. M. Lucocq, and D. R. Alessi. 1998. Mitogen- and stress-activated protein kinase-1 (MSK1) is directly activated by MAPK and SAPK2/p38, and may mediate activation of CREB. The EMBO journal 17:4426-4441. 26. Deng, L., I. Shoji, W. Ogawa, S. Kaneda, T. Soga, D. P. Jiang, Y. H. Ide, and H. Hotta. 2011. Hepatitis C virus infection promotes hepatic gluconeogenesis through an NS5A-mediated, FoxO1-dependent pathway. Journal of virology 85:8556-8568. 27. Dionisio, N., M. V. Garcia-Mediavilla, S. Sanchez-Campos, P. L. Majano, I. Benedicto, J. A. Rosado, G. M. Salido, and J. Gonzalez-Gallego. 2009. Hepatitis C virus NS5A and core proteins induce oxidative stress-mediated calcium signalling alterations in hepatocytes. Journal of hepatology 50:872-882. 28. Douglas, M. W., and J. George. 2009. Molecular mechanisms of insulin resistance in chronic hepatitis C. World journal of gastroenterology : WJG 15:4356-4364. 29. Du, K., and M. Montminy. 1998. CREB is a regulatory target for the protein kinase Akt/PKB. The Journal of biological chemistry 273:32377-32379. 30. Eckart, M. R., M. Selby, F. Masiarz, C. Lee, K. Berger, K. Crawford, C. Kuo, G. Kuo, M. Houghton, and Q. L. Choo. 1993. The hepatitis C virus encodes a serine protease involved in processing of the putative nonstructural proteins from the viral polyprotein precursor. Biochemical and biophysical research communications 192:399-406. 31. Enomoto, N., I. Sakuma, Y. Asahina, M. Kurosaki, T. Murakami, C. Yamamoto, Y. Ogura, N. Izumi, F. Marumo, and C. Sato. 1996. Mutations in the nonstructural protein 5A gene and response to interferon in patients with chronic hepatitis C virus 1b infection. The New England journal of medicine 334:77-81. 32. Failla, C., L. Tomei, and R. De Francesco. 1995. An amino-terminal domain of the hepatitis C virus NS3 protease is essential for interaction with NS4A. Journal of virology 69:1769-1777. 33. Failla, C., L. Tomei, and R. De Francesco. 1994. Both NS3 and NS4A are required for proteolytic processing of hepatitis C virus nonstructural proteins. Journal of virology 68:3753-3760. 34. Gale, M., Jr., C. M. Blakely, B. Kwieciszewski, S. L. Tan, M. Dossett, N. M. Tang, M. J. Korth, S. J. Polyak, D. R. Gretch, and M. G. Katze. 1998. Control of PKR protein kinase by hepatitis C virus nonstructural 5A protein: molecular mechanisms of kinase regulation.Molecular and cellular biology 18:5208-5218. 35. Georgopoulou, U., P. Tsitoura, M. Kalamvoki, and P. Mavromara. 2006. The protein phosphatase 2A represents a novel cellular target for hepatitis C virus NS5A protein. Biochimie 88:651-662. 36. Gong, G., G. Waris, R. Tanveer, and A. Siddiqui. 2001. Human hepatitis C virus NS5A protein alters intracellular calcium levels, induces oxidative stress, and activates STAT-3 and NF-kappa B. Proceedings of the National Academy of Sciences of the United States of America 98:9599-9604. 37. Grakoui, A., D. W. McCourt, C. Wychowski, S. M. Feinstone, and C. M. Rice. 1993. Characterization of the hepatitis C virus-encoded serine proteinase: determination of proteinase-dependent polyprotein cleavage sites. Journal of virology 67:2832-2843. 38. Grakoui, A., D. W. McCourt, C. Wychowski, S. M. Feinstone, and C. M. Rice. 1993. A second hepatitis C virus-encoded proteinase. Proceedings of the National Academy of Sciences of the United States of America 90:10583-10587. 39. Gu, M., and C. M. Rice. 2013. Structures of hepatitis C virus nonstructural proteins required for replicase assembly and function. Current opinion in virology 3:129-136. 40. Han, J. H., V. Shyamala, K. H. Richman, M. J. Brauer, B. Irvine, M. S. Urdea, P. Tekamp-Olson, G. Kuo, Q. L. Choo, and M. Houghton. 1991. Characterization of the terminal regions of hepatitis C viral RNA: identification of conserved sequences in the 5' untranslated region and poly(A) tails at the 3' end. Proceedings of the National Academy of Sciences of the United States of America 88:1711-1715. 41. He, Y., H. Nakao, S. L. Tan, S. J. Polyak, P. Neddermann, S. Vijaysri, B. L. Jacobs, and M. G. Katze. 2002. Subversion of Cell Signaling Pathways by Hepatitis C Virus Nonstructural 5A Protein via Interaction with Grb2 and P85 Phosphatidylinositol 3-Kinase. Journal of virology 76:9207-9217. 42. He, Y., S. L. Tan, S. U. Tareen, S. Vijaysri, J. O. Langland, B. L. Jacobs, and M. G. Katze. 2001. Regulation of mRNA translation and cellular signaling by hepatitis C virus nonstructural protein NS5A. Journal of virology 75:5090-5098. 43. Herzig, S., F. Long, U. S. Jhala, S. Hedrick, R. Quinn, A. Bauer, D. Rudolph, G. Schutz, C. Yoon, P. Puigserver, B. Spiegelman, and M. Montminy. 2001. CREB regulates hepatic gluconeogenesis through the coactivator PGC-1. Nature 413:179-183. 44. Hijikata, M., N. Kato, Y. Ootsuyama, M. Nakagawa, S. Ohkoshi, and K. Shimotohno. 1991. Hypervariable regions in the putative glycoprotein of hepatitis C virus. Biochemical and biophysical research communications 175:220-228. 45. Hijikata, M., N. Kato, Y. Ootsuyama, M. Nakagawa, and K. Shimotohno. 1991. Gene mapping of the putative structural region of the hepatitis C virus genome by in vitro processing analysis. Proceedings of the National Academy of Sciences of the United States of America 88:5547-5551. 46. Hijikata, M., H. Mizushima, T. Akagi, S. Mori, N. Kakiuchi, N. Kato, T. Tanaka, K. Kimura, and K. Shimotohno. 1993. Two distinct proteinase activities required for the processing of a putative nonstructural precursor protein of hepatitis C virus. Journal of virology 67:4665-4675. 47. Hijikata, M., H. Mizushima, Y. Tanji, Y. Komoda, Y. Hirowatari, T. Akagi, N. Kato, K. Kimura, and K. Shimotohno. 1993. Proteolytic processing and membrane association of putative nonstructural proteins of hepatitis C virus. Proceedings of the National Academy of Sciences of the United States of America 90:10773-10777. 48. Hirota, M., S. Satoh, S. Asabe, M. Kohara, K. Tsukiyama-Kohara, N. Kato, M. Hijikata, and K. Shimotohno. 1999. Phosphorylation of nonstructural 5A protein of hepatitis C virus: HCV group-specific hyperphosphorylation. Virology 257:130-137. 49. Honda, M., M. R. Beard, L. H. Ping, and S. M. Lemon. 1999. A phylogenetically conserved stem-loop structure at the 5' border of the internal ribosome entry site of hepatitis C virus is required for cap-independent viral translation. Journal of virology 73:1165-1174. 50. Honda, M., L. H. Ping, R. C. Rijnbrand, E. Amphlett, B. Clarke, D. Rowlands, and S. M. Lemon. 1996. Structural requirements for initiation of translation by internal ribosome entry within genome-length hepatitis C virus RNA. Virology 222:31-42. 51. Huang, Y., K. Staschke, R. De Francesco, and S. L. Tan. 2007. Phosphorylation of hepatitis C virus NS5A nonstructural protein: a new paradigm for phosphorylation-dependent viral RNA replication? Virology 364:1-9. 52. Kaito, M., S. Watanabe, K. Tsukiyama-Kohara, K. Yamaguchi, Y. Kobayashi, M. Konishi, M. Yokoi, S. Ishida, S. Suzuki, and M. Kohara. 1994. Hepatitis C virus particle detected by immunoelectron microscopic study. The Journal of general virology 75 ( Pt7):1755-1760. 53. Kaneko, T., Y. Tanji, S. Satoh, M. Hijikata, S. Asabe, K. Kimura, and K. Shimotohno. 1994. Production of two phosphoproteins from the NS5A region of the hepatitis C viral genome. Biochemical and biophysical research communications 205:320-326. 54. Kasprzak, A., and A. Adamek. 2008. Role of hepatitis C virus proteins (C, NS3, NS5A) in hepatic oncogenesis. Hepatology research : the official journal of the Japan Society of Hepatology 38:1-26. 55. Kato, N., H. Yoshida, S. K. Ono-Nita, J. Kato, T. Goto, M. Otsuka, K. Lan, K. Matsushima, Y. Shiratori, and M. Omata. 2000. Activation of intracellular signaling by hepatitis B and C viruses: C-viral core is the most potent signal inducer. Hepatology 32:405-412. 56. Kawaguchi, T., T. Yoshida, M. Harada, T. Hisamoto, Y. Nagao, T. Ide, E. Taniguchi, H. Kumemura, S. Hanada, M. Maeyama, S. Baba, H. Koga, R. Kumashiro, T. Ueno, H. Ogata, A. Yoshimura, and M. Sata. 2004. Hepatitis C Virus Down-Regulates Insulin Receptor Substrates 1 and 2 through Up-Regulation of Suppressor of Cytokine Signaling 3. The American Journal of Pathology 165:1499-1508. 57. Kim, K., K. H. Kim, E. Ha, J. Y. Park, N. Sakamoto, and J. Cheong. 2009. Hepatitis C virus NS5A protein increases hepatic lipid accumulation via induction of activation and expression of PPARgamma. FEBS letters 583:2720-2726. 58. Kriegs, M., T. Burckstummer, K. Himmelsbach, M. Bruns, L. Frelin, G. Ahlen, M. Sallberg, and E. Hildt. 2009. The hepatitis C virus non-structural NS5A protein impairs both the innate and adaptive hepatic immune response in vivo. The Journal of biological chemistry 284:28343-28351. 59. Lai, C. F., L. Chaudhary, A. Fausto, L. R. Halstead, D. S. Ory, L. V. Avioli, and S. L. Cheng. 2001. Erk is essential for growth, differentiation, integrin expression, and cell function in human osteoblastic cells. The Journal of biological chemistry 276:14443-14450. 60. Lai, M. Y., J. H. Kao, P. M. Yang, J. T. Wang, P. J. Chen, K. W. Chan, J. S. Chu, and D. S. Chen. 1996. Long-term efficacy of ribavirin plus interferon alfa in the treatment of chronic hepatitis C. Gastroenterology 111:1307-1312. 61. Li, X., B. Monks, Q. Ge, and M. J. Birnbaum. 2007. Akt/PKB regulates hepatic metabolism by directly inhibiting PGC-1alpha transcription coactivator. Nature 447:1012-1016. 62. Lim, J. H., H. J. Lee, M. Ho Jung, and J. Song. 2009. Coupling mitochondrial dysfunction to endoplasmic reticulum stress response: a molecular mechanism leading to hepatic insulin resistance. Cellular signalling 21:169-177. 63. Lin, C., and C. M. Rice. 1995. The hepatitis C virus NS3 serine proteinase and NS4A cofactor: establishment of a cell-free trans-processing assay. Proceedings of the National Academy of Sciences of the United States of America 92:7622-7626. 64. Lin, J., C. Handschin, and B. M. Spiegelman. 2005. Metabolic control through the PGC-1 family of transcription coactivators. Cell metabolism 1:361-370. 65. Lohmann, V., F. Korner, U. Herian, and R. Bartenschlager. 1997. Biochemical properties of hepatitis C virus NS5B RNA-dependent RNA polymerase and identification of amino acid sequence motifs essential for enzymatic activity. Journal of virology 71:8416-8428. 66. Lonardo, A., L. E. Adinolfi, P. Loria, N. Carulli, G. Ruggiero, and C. P. Day. 2004. Steatosis and hepatitis C virus: Mechanisms and significance for hepatic and extrahepatic disease. Gastroenterology 126:586-597. 67. Macdonald, A., and M. Harris. 2004. Hepatitis C virus NS5A: tales of a promiscuous protein. The Journal of general virology 85:2485-2502. 68. Majumder, M., R. Steele, A. K. Ghosh, X. Y. Zhou, L. Thornburg, R. Ray, N. J. Phillips, and R. B. Ray. 2003. Expression of hepatitis C virus non-structural 5A protein in the liver of transgenic mice. FEBS letters 555:528-532. 69. Manabe, S., I. Fuke, O. Tanishita, C. Kaji, Y. Gomi, S. Yoshida, C. Mori, A. Takamizawa, I. Yosida, and H. Okayama. 1994. Production of nonstructural proteins of hepatitis C virus requires a putative viral protease encoded by NS3. Virology 198:636-644. 70. Mayr, B., and M. Montminy. 2001. Transcriptional regulation by the phosphorylation-dependent factor CREB. Nature reviews. Molecular cell biology 2:599-609. 71. Mizushima, H., M. Hijikata, Y. Tanji, K. Kimura, and K. Shimotohno. 1994. Analysis of N-terminal processing of hepatitis C virus nonstructural protein 2. Journal of virology 68:2731-2734. 72. Mori, Y., K. Moriishi, and Y. Matsuura. 2008. Hepatitis C virus core protein: its coordinate roles with PA28gamma in metabolic abnormality and carcinogenicity in the liver. The international journal of biochemistry & cell biology 40:1437-1442. 73. Nakano, T., G. M. Lau, G. M. Lau, M. Sugiyama, and M. Mizokami. 2012. An updated analysis of hepatitis C virus genotypes and subtypes based on the complete coding region. Liver international : official journal of the International Association for the Study of the Liver 32:339-345. 74. Noto, H., and P. Raskin. 2006. Hepatitis C infection and diabetes. Journal of diabetes and its complications 20:113-120. 75. Park, J. S., J. M. Yang, and M. K. Min. 2000. Hepatitis C virus nonstructural protein NS4B transforms NIH3T3 cells in cooperation with the Ha-ras oncogene. Biochemical and biophysical research communications 267:581-587. 76. Park, K. J., S. H. Choi, D. H. Choi, J. M. Park, S. W. Yie, S. Y. Lee, and S. B. Hwang. 2003. 1Hepatitis C virus NS5A protein modulates c-Jun N-terminal kinase through interaction with tumor necrosis factor receptor-associated factor 2. The Journal of biological chemistry 278:30711-30718. 77. Parvaiz, F., S. Manzoor, H. Tariq, F. Javed, K. Fatima, and I. Qadri. 2011. Hepatitis C virus infection: molecular pathways to insulin resistance. Virology journal 8:474. 78. Ponugoti, B., G. Dong, and D. T. Graves. 2012. Role of forkhead transcription factors in diabetes-induced oxidative stress. Experimental diabetes research 2012:939751. 79. Puigserver, P., and B. M. Spiegelman. 2003. Peroxisome proliferator-activated receptor-gamma coactivator 1 alpha (PGC-1 alpha): transcriptional coactivator and metabolic regulator. Endocrine reviews 24:78-90. 80. Qadri, I., M. Iwahashi, J. M. Capasso, M. W. Hopken, S. Flores, J. Schaack, and F. R. Simon. 2004. Induced oxidative stress and activated expression of manganese superoxide dismutase during hepatitis C virus replication: role of JNK, p38 MAPK and AP-1. The Biochemical journal 378:919-928. 81. Rennefahrt, U., B. Illert, A. Greiner, U. R. Rapp, and J. Troppmair. 2004. Tumor induction by activated JNK occurs through deregulation of cellular growth. Cancer letters 215:113-124. 82. Rizzetto, M., M. G. Canese, J. L. Gerin, W. T. London, D. L. Sly, and R. H. Purcell. 1980. Transmission of the hepatitis B virus-associated delta antigen to chimpanzees. The Journal of infectious diseases 141:590-602. 83. Rozance, P. J., S. W. Limesand, J. S. Barry, L. D. Brown, S. R. Thorn, D. LoTurco, T. R. Regnault, J. E. Friedman, and W. W. Hay, Jr. 2008. Chronic late-gestation hypoglycemia upregulates hepatic PEPCK associated with increased PGC1alpha mRNA and phosphorylated CREB in fetal sheep. American journal of physiology. Endocrinology and metabolism 294:E365-370. 84. Ryffel, G. U. 2001. Mutations in the human genes encoding the transcription factors of the hepatocyte nuclear factor (HNF)1 and HNF4 families: functional and pathological consequences. Journal of molecular endocrinology 27:11-29. 85. Santolini, E., G. Migliaccio, and N. La Monica. 1994. Biosynthesis and biochemical properties of the hepatitis C virus core protein. Journal of virology 68:3631-3641. 86. Sheikh, M. Y., J. Choi, I. Qadri, J. E. Friedman, and A. J. Sanyal. 2008. Hepatitis C virus infection: molecular pathways to metabolic syndrome. Hepatology 47:2127-2133. 87. Shepard, C. W., L. Finelli, and M. J. Alter. 2005. Global epidemiology of hepatitis C virus infection. The Lancet infectious diseases 5:558-567. 88. Simmonds, P., A. Alberti, H. J. Alter, F. Bonino, D. W. Bradley, C. Brechot, J. T. Brouwer, S. W. Chan, K. Chayama, D. S. Chen, and et al. 1994. A proposed system for the nomenclature of hepatitis C viral genotypes. Hepatology 19:1321-1324. 89. Spaete, R. R., D. Alexander, M. E. Rugroden, Q. L. Choo, K. Berger, K. Crawford, C. Kuo, S. Leng, C. Lee, R. Ralston, K. Thudium, J. W. Tung, G. Kuo, and M. Houghton. 1992. Characterization of the hepatitis C virus E2/NS1 gene product expressed in mammalian cells. Virology 188:819-830. 90. Street, A., A. Macdonald, K. Crowder, and M. Harris. 2004. The Hepatitis C virus NS5A protein activates a phosphoinositide 3-kinase-dependent survival signaling cascade. The Journal of biological chemistry 279:12232-12241. 91. Sun, P., H. Enslen, P. S. Myung, and R. A. Maurer. 1994. Differential activation of CREB by Ca2+/calmodulin-dependent protein kinases type II and type IV involves phosphorylation of a site that negatively regulates activity. Genes & Development 8:2527-2539. 92. Sy, T., and M. M. Jamal. 2006. Epidemiology of hepatitis C virus (HCV) infection. International journal of medical sciences 3:41-46. 93. Tai, C. L., W. K. Chi, D. S. Chen, and L. H. Hwang. 1996. The helicase activity associated with hepatitis C virus nonstructural protein 3 (NS3). Journal of virology 70:8477-8484. 94. Takahashi, K., S. Kishimoto, H. Yoshizawa, H. Okamoto, A. Yoshikawa, and S. Mishiro. 1992. p26 protein and 33-nm particle associated with nucleocapsid of hepatitis C virus recovered from the circulation of infected hosts. Virology 191:431-434. 95. Tan, S. L., H. Nakao, Y. He, S. Vijaysri, P. Neddermann, B. L. Jacobs, B. J. Mayer, and M. G. Katze. 1999. NS5A, a nonstructural protein of hepatitis C virus, binds growth factor receptor-bound protein 2 adaptor protein in a Src homology 3 domain/ligand-dependent manner and perturbs mitogenic signaling. Proceedings of the National Academy of Sciences of the United States of America 96:5533-5538. 96. Tanaka, T., N. Kato, M. J. Cho, and K. Shimotohno. 1995. A novel sequence found at the 3' terminus of hepatitis C virus genome. Biochemical and biophysical research communications 215:744-749. 97. Tanji, Y., T. Kaneko, S. Satoh, and K. Shimotohno. 1995. Phosphorylation of hepatitis C virus-encoded nonstructural protein NS5A. Journal of virology 69:3980-3986. 98. Tellinghuisen, T. L., K. L. Foss, and J. Treadaway. 2008. Regulation of hepatitis C virion production via phosphorylation of the NS5A protein. PLoS pathogens 4:e1000032. 99. Tsukiyama-Kohara, K., N. Iizuka, M. Kohara, and A. Nomoto. 1992. Internal ribosome entry site within hepatitis C virus RNA. Journal of virology 66:1476-1483. 100. Tu, H., L. Gao, S. T. Shi, D. R. Taylor, T. Yang, A. K. Mircheff, Y. Wen, A. E. Gorbalenya, S. B. Hwang, and M. M. Lai. 1999. Hepatitis C virus RNA polymerase and NS5A complex with a SNARE-like protein. Virology 263:30-41. 101. Tzivion, G., M. Dobson, and G. Ramakrishnan. 2011. FoxO transcription factors; Regulation by AKT and 14-3-3 proteins. Biochimica et biophysica acta 1813:1938-1945. 102. van Doorn, L. J., I. Capriles, G. Maertens, R. DeLeys, K. Murray, T. Kos, H. Schellekens, and W. Quint. 1995. Sequence evolution of the hypervariable region in the putative envelope region E2/NS1 of hepatitis C virus is correlated with specific humoral immune responses. Journal of virology 69:773-778. 103. Wang, A. G., D. S. Lee, H. B. Moon, J. M. Kim, K. H. Cho, S. H. Choi, H. L. Ha, Y. H. Han, D. G. Kim, S. B. Hwang, and D. Y. Yu. 2009. Non-structural 5A protein of hepatitis C virus induces a range of liver pathology in transgenic mice. The Journal of pathology 219:253-262. 104. Weiner, A. J., M. J. Brauer, J. Rosenblatt, K. H. Richman, J. Tung, K. Crawford, F. Bonino, G. Saracco, Q. L. Choo, M. Houghton, and et al. 1991. Variable and hypervariable domains are found in the regions of HCV corresponding to the flavivirus envelope and NS1 proteins and the pestivirus envelope glycoproteins. Virology 180:842-848. 105. Wu, S. C., S. C. Chang, H. Y. Wu, P. J. Liao, and M. F. Chang. 2008. Hepatitis C virus NS5A protein down-regulates the expression of spindle gene Aspm through PKR-p38 signaling pathway. The Journal of biological chemistry 283:29396-29404. 106. Xing, J., J. M. Kornhauser, Z. Xia, E. A. Thiele, and M. E. Greenberg. 1998. Nerve growth factor activates extracellular signal-regulated kinase and p38 mitogen-activated protein kinase pathways to stimulate CREB serine 133 phosphorylation. Molecular and cellular biology 18:1946-1955. 107. Yoon, J. C., P. Puigserver, G. Chen, J. Donovan, Z. Wu, J. Rhee, G. Adelmant, J. Stafford, C. R. Kahn, D. K. Granner, C. B. Newgard, and B. M. Spiegelman. 2001. Control of hepatic gluconeogenesis through the transcriptional coactivator PGC-1. Nature 413:131-138. 108. Zampino, R., A. Marrone, L. Restivo, B. Guerrera, A. Sellitto, L. Rinaldi, C. Romano, and L. E. Adinolfi. 2013. Chronic HCV infection and inflammation: Clinical impact on hepatic and extra-hepatic manifestations. World journal of hepatology 5:528-540. 109. 吳舜祺. (2008). Molecular mechanisms of hepatitis C virus NS5A protein involved in the down-regulation of the downstream PKR signaling pathway. 國立台灣大學醫學院生物化學暨分子生物學研究所博士論文 | |
dc.identifier.uri | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/58276 | - |
dc.description.abstract | C 型肝炎病毒 (HCV) 是造成慢性肝炎和肝硬化的主要原因,甚至還
可能會發展成肝癌或第二型糖尿病。C 型肝炎病毒的核心蛋白質和NS5A 蛋白質被認為可能會參與HCV 所造成的第二型糖尿病的發生,但是詳細 的機制目前還尚未了解。利用流體力學為基礎之體內轉染法,建立一個以 老鼠肝細胞短暫表現NS5A 蛋白質的系統,進行微陣列 (microarray) 的分 析研究,找出表現受到NS5A 蛋白質影響的基因。結果發現在表現NS5A 蛋白質的老鼠肝臟細胞中,糖質新生的速率限制酵素PEPCK 的表現增加, 結果亦發現在有糖尿病的C 型肝炎患者。PEPCK 是糖質新生過程的重要 酵素,而且PEPCK 的過量表現會造成肝臟葡萄糖的產生增加。在本研究 中也證實NS5A 蛋白質在原代肝細胞中會促進葡萄糖的產生。PEPCK 基因 啟動子的轉錄活化,受轉錄因子CREB (cyclic AMP response element binding protein) 、FoxO1 (forkhead transcription factor O1) 和HNF-4a (hepatocyte nuclear factor 4a) 的調控,其中FoxO1 和HNF-4a 還需要與共 活化因子PGC-1a 結合才能達到活化PEPCK 基因啟動子的作用。過去的 研究指出,PGC-1a 在肝臟糖質新生的過程中扮演重要的調控角色,而且 可能會參與糖尿病的致病機制。在老鼠肝細胞短暫表現NS5A 蛋白質的系 統中,微陣列的分析結果也看到PGC-1a 基因的表現量增加。在表現NS5A 蛋白質的細胞中和HCV 感染及複製系統 (HCV type 1b subgenomic replicon),藉由即時聚合酶連鎖反應和西方墨點法的分析,都可以看到PEPCK 和 PGC-1a 的表現增加。更進一步的實驗證實,NS5A 蛋白質可 能透過PI3K-Akt 和JNK 之訊息傳遞路徑,正調控PEPCK 和PGC-1a 的 表現。此外,在表現NS5A 蛋白質的細胞中也發現了轉錄因子FoxO1 和 HNF-4a 的表現增加,以及轉錄因子CREB 的磷酸化增加。本研究證實, NS5A 蛋白質可能藉由活化轉錄因子CREB、增加轉錄因子FoxO1 和 HNF-4a 的表現,以及透過PI3K-Akt 和JNK 之訊息傳遞促進PGC-1a 的 表現,進而促進PEPCK 的表現和葡萄糖的產生。推測NS5A 蛋白質可能 藉此參與HCV 所造成的第二型糖尿病的致病機制中。 | zh_TW |
dc.description.abstract | Hepatitis C virus (HCV) is a major cause of chronic hepatitis, liver cirrhosis, and highly associated with hepatocellular carcinoma and type 2 diabetes mellitus (T2DM). The HCV viral proteins, core and NS5A protein, are
thought to be involved in the development of HCV-induced T2DM, but the detailed mechanisms remain unclear. A cDNA microarray analysis with a mouse system with or without NS5A expression following hydrodynamics-based transfection was performed to identify differentially expressed genes. Upregulation of the gluconeogenic rate-limiting enzyme phosphoenolpyruvate carboxykinase (PEPCK) compared with controls was detected in mouse hepatocytes expressing NS5A protein. The result was also found in HCV patients with diabetes. PEPCK is the key enzyme in gluconeogenesis and its over-expression can stimulate hepatic glucose output. Full transcriptional activation of the PEPCK promoter requires transactivation mediated by the cyclic AMP response element binding protein (CREB) and peroxisome proliferator-activated receptor-gamma coactivator-1a (PGC-1a)- mediated coactivation of the glucocorticoid receptor, the forkhead transcription factor O1 (FoxO1), and the hepatocyte nuclear factor 4a (HNF-4a). PGC-1a, a transcriptional coactivator, is a key modulator of hepatic gluconeogenesis likely to be involved in the pathogenesis of diabetes. In this study, an HCV NS5A-mediated dose-dependent increase of glucose production was demonstrated in human primary hepatocytes. Upregulation of PGC-1a compared with controls was also detected in mouse hepatocytes expressing NS5A protein. In addition, the up-regulation of PEPCK and PGC-1a genes were also detected by real-time quantitative polymerase chain reaction and Western blot analysis both in NS5A-expressing cells and in the viral genotype 1b subgenomic replicon system. Further studies demonstrated that the NS5A-mediated upregulation of PEPCK and PGC-1a were resulted from the activation of PI3K-Akt and JNK signaling pathways. In addition, the expression levels of FoxO1 and HNF-4a, and the phosphorylation level of CREB were increased in HCV NS5A-expressing cells. These results suggest that HCV NS5A protein enhances PEPCK expression and stimulates hepatic glucose output by activation of its transactivators FoxO1, HNF-4a, CREB and coactivator PGC-1a mediated by PI3K-Akt and JNK signaling pathways. These data imply that NS5A is involved in the HCV-associated T2DM. | en |
dc.description.provenance | Made available in DSpace on 2021-06-16T08:10:03Z (GMT). No. of bitstreams: 1 ntu-103-D95442002-1.pdf: 2143965 bytes, checksum: 80481af6da714e6ef1035d6a370cee01 (MD5) Previous issue date: 2014 | en |
dc.description.tableofcontents | 中文摘要 ……………………...……………………………I
英文摘要 ….………………………………………………III 緒論 ………….……………………………………….……1 材料來源 …………………………………………………13 實驗方法 …………………………………………………20 實驗結果 …………………………………………………36 討論 ………………………………………………………42 圖表 ………………………………………………………48 參考文獻 ………………………………………..………...63 | |
dc.language.iso | zh-TW | |
dc.title | C型肝炎病毒非結構性蛋白質NS5A參與正調控糖質新生之分子機制 | zh_TW |
dc.title | Molecular Mechanisms of Hepatitis C Virus NS5A Protein Involved in the Upregulation of Gluconeogenesis | en |
dc.type | Thesis | |
dc.date.schoolyear | 102-2 | |
dc.description.degree | 博士 | |
dc.contributor.oralexamcommittee | 張富雄,張智芬,莊立民,楊宏志,林敬哲 | |
dc.subject.keyword | C型肝炎病毒,糖尿病, | zh_TW |
dc.subject.keyword | HCV,gluconeogenesis, | en |
dc.relation.page | 74 | |
dc.rights.note | 有償授權 | |
dc.date.accepted | 2014-04-09 | |
dc.contributor.author-college | 醫學院 | zh_TW |
dc.contributor.author-dept | 生物化學暨分子生物學研究所 | zh_TW |
顯示於系所單位: | 生物化學暨分子生物學科研究所 |
文件中的檔案:
檔案 | 大小 | 格式 | |
---|---|---|---|
ntu-103-1.pdf 目前未授權公開取用 | 2.09 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。