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完整後設資料紀錄
DC 欄位 | 值 | 語言 |
---|---|---|
dc.contributor.advisor | 蔡懷楨(Huai-Jen Tsai) | |
dc.contributor.author | Hao-Chan Lo | en |
dc.contributor.author | 羅浩展 | zh_TW |
dc.date.accessioned | 2021-06-07T17:53:04Z | - |
dc.date.copyright | 2012-08-22 | |
dc.date.issued | 2012 | |
dc.date.submitted | 2012-08-18 | |
dc.identifier.citation | 黃昱愷(2007)。抗心律不整藥物Amiodarone影響斑馬魚胚胎心臟瓣膜的發育。台灣大學分子與細胞生物學研究所碩士論文。
陳大淵(2008)。抗心律不整藥物Amiodarone藉由抑制表皮間質轉換而干擾斑馬魚胚胎心臟瓣膜發育。台灣大學分子與細胞生物學研究所碩士論文。 羅道明(2010)。抗心律不整藥物Amiodarone抑制斑馬魚胚胎心臟瓣膜發育之分子機制。台灣大學分子與細胞生物學研究所碩士論文。 Babatin, M, Lee, SS, Pollak, PT. (2008) Amiodarone hepatotoxicity:review. Current Vascular Pharmacology .6:228-36 Bachelder, RE, Yoon, SO, Franci, C, de Herreros, AG, Mercurio, AM. (2005) Glycogen synthase kinase-3 is an endogenous inhibitor of Snail transcription: implications for the epithelial-mesenchymal transition. The Journal of Cell Biology.168:29-33. Bargout, R, Jankov, A, Dincer, E, Wang, R, Komodromos, T, Ibarra-Sunga, O, Filippatos, G, Uhal, BD. (2000) Amiodarone induces apoptosis of human and rat alveolar epithelial cells in vitro. American Journal of Physiology- Lung Cell Molecular Physiology. 278:L1039-44. Baritussio, A, Marzini, S, Agostini, M, Alberti, A, Cimenti, C, Bruttomesso, D, Manzato, E, Quaglino, D, Pettenazzo, A. (2001) Amiodarone inhibits lung degradation of SP-A and perturbs the distribution of lysosomal enzymes. American Journal of Physiology- Lung Cell Molecular Physiology. 281:L1189-99. Barrallo-Gimeno, A, Nieto, MA. (2005) The Snail genes as inducers of cell movement and survival: implications in development and cancer. Development. 132:3151-61. Bartman, T, Walsh, EC, Wen, KK, McKane, M, Ren, J, Alexander, J, Rubenstein, PA, Stainier, DY. (2004) Early myocardial function affects endocardial cushion development in zebrafish. PLoS Biology. 2:E129 Beis, D, Bartman, T, Jin, SW, Scott, IC, D'Amico, LA, Ober, EA, Verkade, H, Frantsve, J, Field, HA, Wehman, A, Baier, H, Tallafuss, A, Bally-Cuif, L, Chen, J, Stainier, DYR, Jungblut, B. (2005). Genetic and cellular analyses of zebrafish atrioventricular cushion and valve development. Development.132:4193-4204. Butcher, JT, Markwald, RR. (2007). Valvulogenesis: the moving target. Philosophical Transactions of the Royal Society B .362:1489-1503. Camarata, T, Krcmery, J, Snyder, D, Park, S, Topczewski, J, Simon, HG. (2010). Pdlim7 (LMP4) regulation of Tbx5 specifies zebrafish heart atrio-ventricular boundary and valve formation. Developmental Biology .337:233-245. Cano, A, Pérez-Moreno, MA, Rodrigo, I, Locascio, A, Blanco, MJ, del Barrio, MG, Portillo, F, Nieto, MA. (2000). The transcription factor snail controls epithelial-mesenchymal transitions by repressing E-cadherin expression. Nature Cell Biology.2:76-83. Camenisch, TD, Spicer, AP, Brehm-Gibson, T, Biesterfeldt, J, Augustine, ML, Calabro Jr, A., Kubalak, S, Klewer, SE, McDonald, JA. (2000). Disruption of hyaluronan synthase-2 abrogates normal cardiac morphogenesis and hyaluronan-mediated transformation of epithelium to mesenchyme. Journal of Clinical Investigation. 106:349-360. Cheng, W, Guo, L, Zhang, Z, Soo, HM, Wen, C, Wu, W, Peng, J. (2006). HNF factors form a network to regulate liver-enriched genes in zebrafish. Developmental Biolog..294:482-496. Chi, NC, Shaw, RM, De Val, S, Kang, G, Jan, LY, Black, BL, Stainier, DYR. (2008). Foxn4 directly regulates tbx2b expression and atrioventricular canal formation. Genes & Development. 22:734-739. Citri, A, Yarden, Y. (2006) EGF-ERBB signalling: towards the systems level. Nature Reviews Molecular Cell Biology. 7:505-16. De la Cruz, MV, Giménez-Ribotta, M, Saravalli, O, Cayré, R. (1983). The contribution of the inferior endocardial cushion of the atrioventricular canal to cardiac septation and to the development of the atrioventricular valves: study in the chick embryo. American Journal of Anatomy. 166:63-72. Dhomen, NS, Mariadason, J, Tebbutt, N, Scott, AM. (2012) Therapeutic targeting of the epidermal growth factor receptor in human cancer. Critical Reviews in Oncogenesis. 17:31-50. Du, WW, Yang, BB, Shatseva, TA, Yang, BL, Deng, Z, Shan, SW, Lee, DY, Seth, A, Yee, AJ. (2010) Versican G3 promotes mouse mammary tumor cell growth, migration, and metastasis by influencing EGF receptor signaling. PLoS One.5:e13828. Gan, HK, Walker, F, Burgess, AW, Rigopoulos, A, Scott, AM, Johns, TG. (2007). The epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor AG1478 increases the formation of inactive untethered EGFR dimers. Implications for combination therapy with monoclonal antibody 806. The Journal of Biological Chemistry.282:2840-2850. Goishi, K, Lee, P, Davidson, AJ, Nishi, E, Zon, LI, Klagsbrun, M. (2003) Inhibition of zebrafish epidermal growth factor receptor activity results in cardiovascular defects. Mechanisms of Development. 120:811-22. Henderson, DJ, Ybot-Gonzalez, P, Copp, AJ. (1997). Over-expression of the chondroitin sulphate proteoglycan versican is associated with defective neural crest migration in the Pax3 mutant mouse (splotch). Mechanisms of Development. 69:39-51. Henderson, DJ, Copp, AJ.(1998). Versican expression is associated with chamber specification, septation, and valvulogenesis in the developing mouse heart. Circulation Research. 83:523-532. Hernández, D, Miquel-Serra, L, Docampo, M. J., Marco-Ramell, A, Cabrera, J, Fabra, A, Bassols, A. (2011). V3 versican isoform alters the behavior of human melanoma cells by interfering with CD44/ErbB-dependent signaling. Journal of Biological Chemistry. 286:1475-1485. Ikäheimo, K, Kettunen, R, Mäntyjärvi, M. (2002) Visual functions and adverse ocular effects in patients with amiodarone medication. Acta Ophthalmol Scand .80: 59-63 Iwamoto, R, Mekada, E. (2006) ErbB and HB-EGF signaling in heart development and function. Cell Structure and Function. 31:1-14. Kang, JS, Oohashi, T, Kawakami, Y, Bekku, Y, Izpisúa-Belmonte, JC, Ninomiya, Y. (2004). Characterization of dermacan, a novel zebrafish lectican gene, expressed in dermal bones. Mechanisms of Development. 121:301-312. Kato, N, Shimmura, S, Kawakita, T, Miyashita, H, Ogawa, Y, Yoshida, S, Higa, K, Okano, H, Tsubota, K. (2007) Beta-catenin activation and epithelial-mesenchymal transition in the pathogenesis of pterygium. Investigative Ophthalmology and Visual Science. 48:1511-7. Kern, CB, Twal, WO, Mjaatvedt, CH, Fairey, SE, Toole, BP, Iruela-Arispe, ML, Argraves, WS. (2006) Proteolytic cleavage of versican during cardiac cushion morphogenesis. Developmental Dynamics. 235:2238-47. Kodama, I, Kamiya, K, Toyama, J. (1999). Amiodarone: ionic and cellular mechanisms of action of the most promising class III agent. The American Journal of Cardiology .84:20-28. Kokudo, T, Suzuki, Y, Yoshimatsu, Y, Yamazaki, T, Watabe, T, Miyazono, K. (2008). Snail is required for TGFβ-induced endothelial-mesenchymal transition of embryonic stem cell-derived endothelial cells. Journal of Cell Science. 121:3317-3324. Landolt, RM, Vaughan, L, Winterhalter, KH, Zimmermann, DR. (1995). Versican is selectively expressed in embryonic tissues that act as barriers to neural crest cell migration and axon outgrowth. Development. 121: 2303-2312. Lee, HC, Chen, JN, Liao, PY, Tsai, WY, Lin, KY, Chuang, CC, Sun, CK, Chang, WC, Tsai, HJ. (2007). Glycogen synthase kinase 3α and 3β have distinct functions during cardiogenesis of zebrafish embryo. BMC Developmental Biology. 7:93. Lee, MY, Chou, CY, Tang, MJ, Shen, MR.(2008) Epithelial-mesenchymal transition in cervical cancer: correlation with tumor progression, epidermal growth factor receptor overexpression, and snail up-regulation. Clinical Cancer Research.14:4743-50. Martin, RT, Bartman, T. (2009) Analysis of heart valve development in larval zebrafish. Developmental Dynamics. 238:1796-802. Morton, SU, Scherz, PJ, Cordes, KR, Ivey, KN, Stainier, DYR, Srivastava, D. (2008). microRNA-138 modulates cardiac patterning during embryonic development. Proceedings of the National Academy of Sciences ,USA.105:17830-17835. Mjaatvedt, C.H, Yamamura, H, Capehart, AA, Turner, D, Markwald, RR. (1998). The cspg2 gene, disrupted in the hdf mutant, is required for right cardiac chamber and endocardial cushion formation. Developmental Biology .202:56-66. Nguyen, CT, Lu, Q, Wang, Y, Chen, JN. (2008). Zebrafish as a model for cardiovascular development and disease. Drug Discovery Today: Disease Models. 5:135-140. Olayioye, MA, Neve, RM, Lane, HA, Hynes, NE. (2000) The ErbB signaling network: receptor heterodimerization in development and cancer. The EMBO Journal. 19:3159-67. Peal, DS, Burns, CG, Macrae, CA, Milan, D. (2009). Chondroitin sulfate expression is required for cardiac atrioventricular canal formation. Developmental Dynamics .238:3103-3110. Qu, X, Jia, H, Garrity, DM, Tompkins, K, Batts, L, Appel, B, Zhong, TP, Baldwin, HS. (2008). Ndrg4 is required for normal myocyte proliferation during early cardiac development in zebrafish. Developmental Biology .317:486-496. Ricciardelli, C, Sakko, AJ, Ween, MP, Russell, DL, Horsfall, DJ. (2009). The biological role and regulation of versican levels in cancer.Cancer Metastasis Review. 28:233-245. Roden, DM. (2000). Antiarrhythmic drugs: from mechanisms to clinical practice. Heart. 84:339-346. Sanchez-Soria, P, Camenisch, TD. (2010) ErbB signaling in cardiac development and disease. Seminars in Cell and Developmental Biology. 21:929-35 Savagner, P. (2001) Leaving the neighborhood: molecular mechanisms involved during epithelial-mesenchymal transition. Bioessays.23:912-23 Scherz, PJ, Huisken, J, Sahai-Hernandez, P, Stainier, DYR. (2008). High-speed imaging of developing heart valves reveals interplay of morphogenesis and function. Development .135:1179-1187. Schrijver, I, Liu, W, Brenn, T, Furthmayr, H, Francke, U. (1999). Cysteine substitutions in epidermal growth factor-like domains of fibrillin-1: distinct effects on biochemical and clinical phenotypes. The American Journal of Human Genetics. 65:1007-20. Sheng, W, Wang, G, Wang, Y, Liang, J, Wen, J, Zheng, PS, Wu, Y, Lee, V, Slingerland, J, Dumont, D, Yang, BB. (2005). The roles of versican V1 and V2 isoforms in cell proliferation and apoptosis. Molecular Biology of the Cell. 16:1330-1340. Sheng, W, Wang, G, La Pierre, DP, Wen, J, Deng, Z, Wong, CKA, Lee, DY, Yang, BB. (2006). Versican mediates mesenchymal-epithelial transition. Molecular Biology of the Cell. 17:2009-2020. Singh, SN, Fletcher, RD, Fisher, SG, Singh, BN, Lewis, HD, Deedwania, PC, Massie, BM, Colling, C, Lazzeri, D. (1995) Amiodarone in patients with congestive heart failure and asymptomatic ventricular arrhythmia. The New England Journal of Medicine.333: 77-82 Stainier, DYR. (2001). Zebrafish genetics and vertebrate heart formation. Nature Reviews Genetics .2:39-48. Stankunas, K, Hang, CT, Tsun, ZY, Chen, H, Lee, NV, Wu, JI, Shang, C, Bayle, JH, Shou, W, Iruela-Arispe, ML, Chang, CP. (2008). Endocardial Brg1 represses ADAMTS1 to maintain the microenvironment for myocardial morphogenesis. Developmental Cell .14:298-311. Suwan, K, Choocheep, K, Hatano, S, Kongtawelert, P, Kimata, K, Watanabe, H. (2009). Versican/PG-M Assembles Hyaluronan into Extracellular Matrix and Inhibits CD44-mediated Signaling toward Premature Senescence in Embryonic Fibroblasts. Journal of Biological Chemistry. 284:8596-8604. Thiery, JP, Sleeman, JP. (2006) Complex networks orchestrate epithelial- mesenchymal transitions. Nature Reviews Molecular Cell Biology. 7:131-42 Thisse, C, Thisse, B. (1999). Antivin, a novel and divergent member of the TGFβ superfamily, negatively regulates mesoderm induction. Development. 126:229-240. Tu, CT, Yang, TC, Tsai, HJ. (2009). Nkx2. 7 and Nkx2. 5 Function Redundantly and Are Required for Cardiac Morphogenesis of Zebrafish Embryos. PLoS One 4:e4249. Vidal, F, De Araujo, WM, Cruz, AL, Tanaka, MN, Viola, JP, Morgado-Díaz, JA. (2011). Lithium reduces tumorigenic potential in response to EGF signaling in human colorectal cancer cells. International Journal Oncology. 38:1365-1373. Walsh, EC, Stainier, DYR. (2001). UDP-glucose dehydrogenase required for cardiac valve formation in zebrafish. Science .293:1670-1673. Wasa, J, Nishida, Y, Shinomura, T, Isogai, Z, Futamura, N, Urakawa, H, Arai, E, Kozawa, E, Tsukushi, S, Ishiguro, N. (2012). Versican V1 isoform regulates cell-associated matrix formation and cell behavior differentially from aggrecan in Swarm rat chondrosarcoma cells. International Journal of Cancer. 130:2271-2281. Wight, TN.(2002). Versican: a versatile extracellular matrix proteoglycan in cell biology Current Opinion in Cell Biology. 14:617-23. Yarden, Y, Sliwkowski, MX. (2001) Untangling the ErbB signalling network. Nature Reviews Molecular Cell Biology. 2:127-37. Yee, AJ, Akens, M, Yang, BL, Finkelstein, J, Zheng, PS, Deng, Z, Yang, B. (2007). The effect of versican G3 domain on local breast cancer invasiveness and bony metastasis. Breast Cancer Research. 9:R47. Zhang, Y, Cao, L, Yang, BL, Yang, BB (1998). The G3 domain of versican enhances cell proliferation via epidermial growth factor-like motifs. Journal of Biological Chemistry. 273:21342-21351. Zhang, Y, Cao, L, Kiani, C, Yang, BL, Hu, W, Yang, BB.(1999) Promotion of chondrocyte proliferation by versican mediated by G1 domain and EGF-like motifs. Journal of Cellular Biochemistry. 73:445-57. Zheng, PS, Wen, J, Ang, LC, Sheng, W, Viloria-Petit, A, Wang, Y, Wu, Y, Kerbel, RS, Yang, BB.(2004) Versican/PG-M G3 domain promotes tumor growth and angiogenesis. The FASEB Journal 18:754-6. Zimmermann, DR, Ruoslahti, E. (1989). Multiple domains of the large fibroblast proteoglycan, versican. The EMBO Journal. 8:2975-2981. | |
dc.identifier.uri | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/15829 | - |
dc.description.abstract | Amiodarone一種抗心律不整藥物會誘導斑馬魚胚胎心臟s-vcanb增加,抑制snail-1b在AV canal的表現,造成cdh-5異位性過量增加而導致endocardial cell無法進行invagination,最後造成心臟瓣膜的缺失。然而,在myocardium的s-vcanb如何經過cardiac jelly而影響endocardium的invagination其受器以及分子機制尚未清楚。首先我們注射多量失去功能的dominant-negative form的s-vcanb (dn-s-vcanb)至胚胎中,結果顯示在心臟無法抑制snail-1b的表現,而使snail-1b以及cdh-5的表現與wild-type類似;表示myocardial cell中的S-vcanb透過其蛋白上的domain而影響endocardial cell中的snail-1b以及cdh-5。當我們注射vcana MO,發現抑制vcana不影響正常snail-1b與cdh-5在AV canal的表現,也不影響Amiodarone的結果。所以,我們證明Amiodarone 增加S-vcanb表現是透過其蛋白上的domain而誘導訊息傳導路徑影響下游基因的表現,而vcana則否。另一方面,若用receptor inhibitor,發現其下游snail-1b不在斑馬魚胚胎心臟表現,使得cdh-5不受抑制而增加,其結果與浸泡Amiodarone的胚胎相同;顯示Amiodarone促使S-vcanb過量表現後,S-vcanb會與receptor結合使之呈現dimer狀態,而抑制活性。進一步,我們發現不論是浸泡Amiodarone或是receptor inhibitor皆會讓GSK3β磷酸化程度下降;若將胚胎注射s-vcanb MO並浸泡Amiodarone,發現GSK3β磷酸化就不會下降。綜合以上證據 ,我們的總結是Amiodarone使斑馬魚胚胎心臟myocardium增加S-vcanb表現,蛋白分泌至cardiac jelly後,抑制receptor signaling,使得GSK3β因磷酸化下降而增加活性,進而抑制了snail-1b的表現,使cdh-5過量增加,導致endocardial cell進行invagination受阻,前後造成斑馬魚心臟瓣膜缺失。 | zh_TW |
dc.description.abstract | Amiodarone, an anti-arrhythmia drug, stimulates s-vcanb over-expression at zebrafish embryonic heart, promotes cdh-5 over-expression by inhibited snail-1b at AV canal, and causes invagination of endicardial cell is block to form cardiac valve. However, the receptor and mechanism of s-vcanb affected endocardium invagination through cardiac jelly is still unknown. First, we inject large amount of dominant-negative form of s-vcanb (dn-s-vcanb) into embryo, over-expression of dn-s-vcanb embryos can not inhibit snail-1b expression in the heart field, whereas snail-1b and cdh-5 expression pattern are similar to wild-type; indicating S-vcanb in myocardial cell affects the expression of snail-1b and cdh-5 in endocardial cell by domain. When inject vcana MO, we found that snail-1b and cdh-5 expression in wild-type and Amiodarone-treated embryo was not affected by knockdown vcana. So, we prove that S-vcanb, but not vcana, via domain affect expression of downstream gene in endocardium. Next; Using receptor inhibitor, we found expression of snail-1b at AV canal was missing, and making cdh-5 over-expression, similar to Amiodarone-treated embryo and overexpression wild-type s-vcanb embryo. Therefore, we suggesting that Amiodarone induce over-expression of S-vcanb, then S-vcanb bind to receptor but inhibit receptor activity. Moreover, we found that phosphorylation of GSK3β was decresased in Amiodarone-treated embryo and receptor inhibitor-treated embryo; while Amiodaorone-treated embryo inject with s-vcanb MO, phosphorylation of GSK3β was not decreased; indicating Amiodarone inhibit receptor signaling by inducing s-vcanb over-expression, promoting GSK3β activity, and causing cdh-5 over-expression by suppressing snail-1b. Taken together, we concluded that Amiodarone induces s-vcanb overexpression at myocardium, Amiodarone stimulates S-vcanb overpression and inhibits receptor signaling, elevates GSK3β activity by decreasing its phosphorylation, and causes cdh-5 over-expression by inhibited snail-1b, with in turn, the invagination of endocardial cell is blocked, resulting defect of zebrafish cardiac valve. | en |
dc.description.provenance | Made available in DSpace on 2021-06-07T17:53:04Z (GMT). No. of bitstreams: 1 ntu-101-R99b43009-1.pdf: 2841720 bytes, checksum: 34a67d4b1e7c9c89dffd9fcd91e7c9cb (MD5) Previous issue date: 2012 | en |
dc.description.tableofcontents | 目錄
中文摘要 ………………………………………………………………1 英文摘要 ………………………………………………………………2 文獻回顧 ………………………………………………………………4 前言 …………………………………………………………………10 實驗材料與方法 ……………………………………………………12 結果 …………………………………………………………………19 討論 …………………………………………………………………25 總結 …………………………………………………………………30 參考文獻 ……………………………………………………………31 圖表 …………………………………………………………………42 | |
dc.language.iso | zh-TW | |
dc.title | 抗心律不整藥物Amiodarone抑制斑馬魚胚胎
心臟瓣膜發育之受器與其調控機制 | zh_TW |
dc.title | The Receptor and Regulatory Mechanism of Amiodarone, an Anti-arrhythmia Drug, to Inhibit the Cardiac Valves Formation during the Embryogenesis of Zebrafish | en |
dc.type | Thesis | |
dc.date.schoolyear | 100-2 | |
dc.description.degree | 碩士 | |
dc.contributor.oralexamcommittee | 白麗美,林麗鳳,林芸薇 | |
dc.subject.keyword | 抗心律不整藥物,瓣膜發育, | zh_TW |
dc.subject.keyword | Anti-arrhythmia Drug,valve development, | en |
dc.relation.page | 56 | |
dc.rights.note | 未授權 | |
dc.date.accepted | 2012-08-19 | |
dc.contributor.author-college | 生命科學院 | zh_TW |
dc.contributor.author-dept | 分子與細胞生物學研究所 | zh_TW |
顯示於系所單位: | 分子與細胞生物學研究所 |
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