請用此 Handle URI 來引用此文件：
http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/10651完整後設資料紀錄
| DC 欄位 | 值 | 語言 |
|---|---|---|
| dc.contributor.advisor | 朱善德 | |
| dc.contributor.author | Wei Pan | en |
| dc.contributor.author | 潘暐 | zh_TW |
| dc.date.accessioned | 2021-05-20T21:46:55Z | - |
| dc.date.available | 2010-08-10 | |
| dc.date.available | 2021-05-20T21:46:55Z | - |
| dc.date.copyright | 2010-08-10 | |
| dc.date.issued | 2010 | |
| dc.date.submitted | 2010-08-04 | |
| dc.identifier.citation | 1. Bratt T (2000) Lipocalins and cancer. Biochim Biophys Acta 1482:318–326
2. Flower, D. R. (1996) The lipocalin protein family: structure and function. Biochem. J. 318,1–14 3. Flower, D. R., North, A. C. and Sansom, C. E. (2000) The lipocalin protein family: structural and sequence overview. Biochim. Biophys. Acta 1482, 9–24 4. Flower, D. R. (2000) Beyond the superfamily: the lipocalin receptors. Biochim. Biophys. Acta. 1482, 327–336 5. Harba-Renevey, S., et al., SV40-induced expression of mouse gene 24p3 involves a post-transcriptional mechanism. Oncogene, 1989. 4(5): p. 601-8 6. Flower, D.R., A.C. North, and T.K. Attwood, Mouse oncogene protein 24p3 is a member of the lipocalin family. Biochem Biophys Res Commun, 1991. 180(1): p. 69-74 7. Quansheng Liu and Marit Nilson-Hamilton, Identification of a New Acute Phase Protein. THE JOURNAL OF BIOLOGICAL CHEMISTRY, 1995. Pp. 22565-22570 8. Meheus LA, Fransen LM, Raymackers JG, Blockx HA, Van Beeumen JJ, Van Bun SM & Van de Voorde A 1993, Identification by microsequencing of lipopolysaccharide-induced proteins secreted by mouse macrophages. J immunol 151 1535-1547. 9. Kjeldsen, L., et al., Isolation and primary structure of NGAL, a novel protein associated with human neutrophil gelatinase. J Biol Chem, 1993. 268(14): p.10425-32 10. Kjeldsen L, Bainton DF, Sengelov H, Borregaard N. 1994 Identification of neutrophil gelatinase-associated lipocalin as a novel matrix protein of specific granules in human neutrophils. Blood 83, 799–807. 11. Klausen et al.On mouse and man: neutrophil gelatinase associated lipocalin is not involved in apoptosis or acute response. Eur J Haematol 2005: 75: 332–340. 12. Nilands JB. 1995 Siderophores: structure and function of microbial iron transport compounds. J Biol Chem 270,26723–26726. 13. Strong RK, Bratt T, Cowland JB, Borregaard N, Wiberg FC, Ewald AJ. 1998 Expression, purification, crystallization and crystallographic characterization of dimeric and monomeric human neutrophil gelatinase associated lipocalin ( NGAL). Acta Crystallogr D Biol Crystallogr 54(Pt 1), 93–95. 14. Flo TH, Smith KD, Sato S, et al. 2004 Lipocalin 2 mediates an innate immune response to bacterial infection by sequestrating iron. Nature 432, 917–921. 15. Holmes MA, Paulsene W, Jide X, Ratledge C, Strong RK. 2005 Siderocalin (Lcn 2) also binds carboxymycobactins, potentially defending against mycobacterial infections through iron sequestration. Structure (Camb) 13, 29–41. 16. Devireddy LR, Teodoro JG, Richard FA & Green MR 2001, Induction of apoptosis by a secreted lipocalin that is transcriptionally regulated by IL-3 deprivation. Science 293 829-834. 17. Lin HH, Li WW ,Lee YC & Chu ST 2007, Apoptosis induced by uterine 24p3 protein in endometrial carcinoma cell line. Toxicology 234 203-215. 18. Bong JJ, Seol MB, Kim HH, Han O, Back K & Baik M 2004, The 24p3 gene is induced during involution of the mammary gland and induces apoptosis of mammary epithelial cells. 19. Devireddy, L.R., et al., A cell-surface receptor for lipocalin 24p3 selectively mediates apoptosis and iron uptake. Cell, 2005. 123(7): p. 1293-305 20. Sorensen, O. E., Cowland, J. B., Theilgaard-Monch, K., Liu, L., Ganz, T. and Borregaard, N. (2003) Wound healing and expression of antimicrobial peptides/ polypeptides in human keratinocytes, a consequence of common growth factors. J. Immunol. 170, 5583–5589 21. Nielsen, B. S., Borregaard, N., Bundgaard, J. R., Timshel, S., Sehested, M. and Kjeldsen, L. (1996) Induction of NGAL synthesis in epithelial cells of human colorectal neoplasia and inflammatory bowel diseases. Gut 38, 414–420 22. Stoesz, S. P., Friedl, A., Haag, J. D., Lindstrom, M. J., Clark, G. M. and Gould, M. N. (1998) Heterogeneous expression of the lipocalin NGAL in primary breast cancers. Int. J. Cancer 79, 565–572 23. Furutani, M., Arii, S., Mizumoto, M., Kato, M. and Imamura, M. (1998) Identification of a neutrophil gelatinase-associated lipocalin mRNA in human pancreatic cancers using a modified signal sequence trap method. Cancer Lett. 122, 209–214 24. Bartsch, S. and Tschesche, H. (1995) Cloning and expression of human neutrophil lipocalin cDNA derived from bone marrow and ovarian cancer cells. FEBS Lett. 357, 255–259 25. Iannetti A, Pacifico F, Acquaviva R, Lavorgna A, Crescenzi E, Vascotto C, Tell G, Salzano AM, Scaloni A, Vuttariello E, Chiappetta G, Formisano S, Leonardi A.(2008), The neutrophil gelatinase-associated lipocalin (NGAL), a NF-kappaB-regulated gene, is a survival factor for thyroid neoplastic cells. PNAS. 105, 14058–14063 26. Bauer M, Eickhoff JC, Gould MN, Mundhenke C, Maass N, Friedl A. Neutrophil gelatinase-associated lipocalin (NGAL) is a predictor of poor prognosis in human primary breast cancer. Breast Cancer Res Treat 2008;108:389–97. 27. Xiaohong Leng, et al, Inhibition of Lipocalin 2 Impairs Breast Tumorigenesis and Metastasis. Cancer Res 2009;69(22):8579–84 28. Z. Tong et al., Neutrophil Gelatinase–Associated Lipocalin: A Novel Suppressor of Invasion and Angiogenesis in Pancreatic Cancer. Cancer Res 2008;68(15):6100–8. 29. Hu L, Hittelman W, Lu T, et al. NGAL decreases Ecadherin- mediated cell-cell adhesion and increases cell motility and invasion through Rac1 in colon carcinoma cells. Lab Invest 2009;89:531–48. 30. Yang J, Bielenberg DR, Rodig SJ, et al. Lipocalin 2 promotes breast cancer progression. Proc Natl Acad Sci USA 2009;106:3913–8. 31. Kubben FJ, Sier CF, Hawinkels LJ, et al. Clinical evidence for a protective role of lipocalin-2 against MMP-9 autodegradation and the impact for gastric cancer. Eur J Cancer 2007;43:1869–76 32. Fernandez, C.A., et al., The matrix metalloproteinase-9/neutrophil gelatinase-associated lipocalin complex plays a role in breast tumor growth and is present in the urine of breast cancer patients. Clin Cancer Res, 2005. 11(15):p. 5390-5. 33. Hemdahl, A.L., et al., Expression of neutrophil gelatinase-associated lipocalin in atherosclerosis and myocardial infarction. Arterioscler Thromb Vasc Biol, 2006. 26(1): p. 136-42 34. Biezeveld, M.H., et al., Sustained activation of neutrophils in the course of Kawazaki disease: an association with matrix metalloproteinases. Clin Exp Immunol, 2005. 141(1): p. 183-8. 35. Xu, S. and P. Venge, Lipocalins as biochemical markers of disease. Biochim Biophys Acta, 2000. 1482(1-2): p. 298-307. 36. Mishra, J., et al., Amelioration of ischemic acute renal injury by neutrophil gelatinase-associated lipocalin. J Am Soc Nephrol, 2004. 15(12): p. 3073-82. 37. Vinuesa E, Sola A, Jung M, Alfaro V, Hotter G. Lipocalin-2-induced renal regeneration depends on cytokines. Am J Physiol Renal Physiol 295: F1554–F1562, 2008 38. Yang, J., et al., An iron delivery pathway mediated by a lipocalin. Mol Cell, 2002. 10(5): p. 1045-56 39. Yang, J., et al., Iron, lipocalin, and kidney epithelia. Am J Physiol Renal Physiol, 2003. 285(1): p. F9-18 40. Lee, S., et al., Lipocalin-2 Is an Autocrine Mediator of Reactive Astrocytosis. The Journal of Neuroscience, 2009 • 29(1):234 –249 41. Farina C, Aloisi F, Meinl E., Astrocytes are active players in cerebral innate immunity. Trends Immunol , 2007. 28:138 –145. 42. Kimmel, C.B., et al., Stages of Embryonic Development of the Zebrafish. DEVELOPMENTAL DYNAMICS, 1995. 203:255-310 43. Finlay, B.L. and Darlington, R.B., 1995. Linked regularities in the development and evolution of mammalian brains. Science 268, pp. 1578–1584. 44. Ashwell, K.W., Waite, P.M. and Marotte, L., 1996. Ontogeny of the projection tracts and commissural fibres in the forebrain of the tammar wallaby (Macropus eugenii): timing in comparison with other mammals. Brain Behav. Evol. 47, pp. 8–22. 45. Caviness VS (1982) Neocortical histogenesis in the normal and reeler mice: a developmental study based upon [3H]-thymidine autoradiography. Dev Brain Res 4:293–302. | |
| dc.identifier.uri | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/10651 | - |
| dc.description.abstract | Lcn2是疏水性結合蛋白家族的一員，初期研究被認為是一急性期蛋白，許多的研究指出其參與了多種生理功能，包括免疫功能、細胞凋亡、細胞分化與增生與各種疾病的發生等。近期的研究則多集中於該蛋白與癌症之間的關係。由於先前有研究指出Lcn2參與了胚胎期的腎臟發育，本實驗著重於探討Lcn2在斑馬魚與小鼠的胚胎發育時的表現，利用RT-PCR技術與即時定量PCR分析了Lcn2基因在斑馬魚及小鼠各組織及不同胚胎期Lcn2的表現，發現在斑馬魚的胚胎受精後10小時開始表現，並持續表現到72小時。此外以小鼠為動物模式將研究重點集中於胚胎期腦部的發育過程Lcn2基因的表現時，利用RT-PCR與qPCR的技術，觀察了在不同胚胎期的腦部Lcn2的表現量，結果發現E10.5即有Lcn2基因的表現，但E16.5的胚胎腦部Lcn2基因表現量下降，到E18.5後表現量又恢復，在成鼠亦能持續表現。利用免疫沉澱法與西方墨點術觀察Lcn2蛋白的表現也有類似的結果，但在不同時期的胚胎腦組織中，Lcn2蛋白表現量不多且不具顯著的差異。利用免疫染色法則無法觀察到小鼠胚胎期的腦部組織切片有Lcn2蛋白的表現，推測Lcn2基因在小鼠胚胎期的腦部表現量很低。Lcn2是否在發育過程中有重要功能則仍有待進一步的研究。 | zh_TW |
| dc.description.abstract | Lcn2 is a member of the lipocalin family and has been well known as an acute phase protein. Several evidences showed that Lcn2 is a multi-function protein, participating in such as immunity, apoptosis, ion transport, cell differenciation and proliferation. It may also be related to the occurrence of diseases. Subsequently, it has been found that the expression of Lcn2 gene triggered embryonic kidney development. The finding encourages us to characterize the Lcn2 expression in zebrafish and mice, and look for an animal model to elucidate the biological function of Lcn2. The mRNA level of Lcn2 in tissue distribution and stage profile of embryos in zebrafish and mice were analyzed by RT-PCR and Real-time PCR. Western blotting and immunohistochemical staining have performed for protein assay. The data showed that Lcn2 gene expression initiated in 10 hpf embryo and sustained till 72 hpf. Furthermore, with a mouse brain model, Lcn2 expressed in E10.5, decreased significantly in E16.5 but regained in E18.5, and expressed persistently in the mature mice. The results of immunoprecipitation and Western blotting technique coincided with the mRNA levels in these periods. Unfortunately, we did not find a significant protein expression in between the each stage of embryonic development, and neither in immunohistochemistry analysis. The data revealed that Lcn2 gene expressed in low level during the mouse brain development. | en |
| dc.description.provenance | Made available in DSpace on 2021-05-20T21:46:55Z (GMT). No. of bitstreams: 1 ntu-99-R97b46026-1.pdf: 1313876 bytes, checksum: a88f72b30210e2c3603f4230db2190a4 (MD5) Previous issue date: 2010 | en |
| dc.description.tableofcontents | 謝辭 i
摘要 ii Abstract iii 縮寫表 iv 目錄 vii 第一章 緒論 1 關於Lcn2 1 Lcn2與急性期反應 (Acute phase response, APR) 1 NGAL為人類的Lcn2 1 Lcn2與細胞凋亡 2 Lcn2與細胞存活 3 Lcn2與癌症的關聯 4 Lcn2廣泛的表現與多功能 5 實驗目標 6 第二章 材料與方法 7 材料 7 實驗方法 7 一、樣本組織的擷取與收集 7 二、RNA萃取 8 三、洋菜膠電泳 (Agarose gel electrophoresis) 9 四、反轉錄（Reverse transcription） 10 五、聚合酶連鎖反應PCR（polymerase chain reaction） 11 六、即時定量聚合酶連鎖反應（Quantitative Real-time PCR） 12 七、組織蛋白質萃取 13 八、Pierce 660 nm 蛋白質定量法 13 九、十二酯硫酸鈉-聚丙烯醯胺膠體電泳（SDS-Polyacrylamide gel electrophoresis） 14 十、西方墨點 (western blotting) 15 十一、免疫沉澱法（immunoprecipitation） 17 十二、石蠟包埋 17 十三、免疫組織化學染色法（immunohistochemistry） 19 第三章 結果 21 Lcn2基因在斑馬魚各組織中的表現 21 Lcn2基因在斑馬魚胚胎不同時期的表現 21 Lcn2基因在小鼠各組織中的表現 22 Lcn2基因在小鼠胚胎不同時期腦部的表現 22 Lcn2蛋白在小鼠胚胎不同時期腦部的表現 23 Lcn2蛋白在不同時期胚胎腦部表現的位置 24 第四章 討論 25 第五章 實驗圖表 28 圖一、Lcn2基因在成熟斑馬魚組織中的分佈 28 圖二、斑馬魚胚胎發育過程中不同時期之Lcn2的表現 29 圖三、Lcn2在成熟小鼠組織中的分佈 30 圖四、小鼠胚胎發育過程中不同時期之胚胎腦部的Lcn2基因表現 31 圖五、小鼠不同胚胎期腦部Lcn2基因的表現，以即時定量PCR觀察 32 圖六、小鼠在不同胚胎期腦部之Lcn2蛋白質的表現量 33 圖七、小鼠在不同胚胎期腦部之Lcn2蛋白表現位置 34 附圖 35 附錄 37 參考文獻 39 | |
| dc.language.iso | zh-TW | |
| dc.title | 分泌性Lcn2蛋白在斑馬魚與小鼠腦部組織基因表現的研究 | zh_TW |
| dc.title | Identification of Lcn2 gene expression in zebrafish and mouse brain | en |
| dc.type | Thesis | |
| dc.date.schoolyear | 98-2 | |
| dc.description.degree | 碩士 | |
| dc.contributor.oralexamcommittee | 張?仁,余榮熾,曾婉芳 | |
| dc.subject.keyword | 發育, | zh_TW |
| dc.subject.keyword | Lcn2, | en |
| dc.relation.page | 45 | |
| dc.rights.note | 同意授權(全球公開) | |
| dc.date.accepted | 2010-08-05 | |
| 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-99-1.pdf | 1.28 MB | Adobe PDF | 檢視/開啟 |
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。