由神經生長因子誘導之細胞內訊號路徑活化的化學基因體學分析

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：18

、訪客IP：3.22.217.176

姓名

蔡濟謙(CHI CHIEN) 查詢紙本館藏

畢業系所

系統生物與生物資訊研究所

論文名稱

由神經生長因子誘導之細胞內訊號路徑活化的化學基因體學分析
(Analysis of NGF induced activity of pathways through microarray conjunction with chemical genomics)

相關論文

★ 發展酵素非限制性全基因體調控因子解析方法	★ 大腸癌細胞株之 EGFR—K-ras 訊號路徑的基因微陣列實驗與化學基因體學分析
★ 小鼠胚胎幹細胞株之建立及人類誘導多能性幹細胞之培養技術	★ 細胞週期蛋白D1 mRNA在小鼠胚胎及成體幹細胞和腫瘤細胞中的表現及其受多能性相關因子影響之探討
★ 運用時間序列微陣列資料來預測調控基因	★ 以大鼠嗜鉻性瘤細胞株建立神經訊號傳遞之細胞分子生物學模型
★ 運用高通量基因微矩陣列方法解析由嗜鉻細胞分化成神經細胞之全基因體的調控	★ 神經生長因子在神經分化中轉錄因子活性及基因調控機制之橫觀
★ 以CRSBP-1接合子調控巨噬細胞的移動及吞噬	★ Chemogenomic and Molecular Analysis of Signal Transduction Pathways in In Vivo and In Vitro Models
★ 探討人類子宮內膜 L-selectin ligands 在月經週期的表現

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]

至系統瀏覽論文 ( 永不開放)

摘要(中)

KEGG 資料庫是以分子生物學 (molecular biology)和化學元素互補形成的化學基因體學 (chemical genomics)資料作為其建構網路之基礎，連結基因體資訊和高階功能性資訊，從系統層面分析基因功能的資料庫。我們利用 KEGG 資料庫對實驗室之前 PC12 細胞經 NGF 誘導神經分化的微陣列 (microarray)晶片實驗資料進行系統生物學分析及生物功能路徑註釋。在我們的研究中發現，受 NGF 活化後，無論是整體基因數或神經細胞分化相關路徑中活化基因數都隨 NGF 作用時間而增加；Neurotrophin signaling pathway 於 NGF treated 後 1 小時內雖然可觀察到 Trk 訊號路徑活化的 p38 之基因一時性活化，但是與 1 小時至 3 小時結果相比較，整體路徑的活化有顯著增強，而 MAPK signaling pathway 也隨 NGF 作用時間而呈現明顯的整體路徑活化趨勢；本研究嘗詴了將基因晶片實驗資料以生物網路型式來詮釋複雜的生物系統的可行性，為將來利用生物路徑進行系統生物學研究提供了可行性依據。

摘要(英)

KEGG database is based on networks derived from the interrelation between the molecular biology and the underlying chemical elements. This network database allows scientist to analyze the biological network structure, the genomic information and higher order functional information from a systemic level.
We used KEGG database to study the NGF induced neuronal differentiation of PC12 cells through systems biology analysis and annotation of biological function of signal pathway after microarray experiments. In our study, we found that both the overall number of genes or genes associated with neural cell differentiation in the pathway are increased after the NGF stimulation.
Activation of Trk signaling pathways of p38 gene gradually increased between 1 and 3 hours , along with the activation of the MAPK signaling pathway. This study, though the experimental data of gene chips and bio-network, tried to explore the feasibility of using biological pathway studies though the high through-put method to study the complex biological systems.

關鍵字(中)

★ 微陣列晶片
★ 化學基因體學
★ 神經生長因子

關鍵字(英)

★ microarray
★ chemical genomics
★ NGF

論文目次

目錄
摘要 i
Abstract ii
致謝 iii
第一章緒論 1
1-1現今系統生物學對生物系統的解讀 1
1-2 微陣列晶片 (microarray)和其解讀工具介紹 3
1-3 Kyoto Encyclopedia of Genes and Genomes (KEGG)資料庫介紹 5
1-4神經生長因子於神經分化模型簡介 7
第二章實驗材料與方法 10
2-1基因晶片實驗資料來源 10
2-1-1- 大鼠嗜鉻性瘤細胞培養 10
2-1-2 繼代培養 10
2-1-3 神經生長因子作用實驗 11
2-1-4 RNA萃取 11
2-1-5 基因晶片實驗 12
2-2資料整理 12
2-2-1 變異數分析 (analysis of variance) 12
2-2-2 叢集 (clustering) 13
2-3 KEGG生物路徑資料庫分析 14
2-3-1資料格式化 14
2-3-2資料輸入 14
2-3-3 KegArray軟體應用與資料庫建立 14
2-3-3-2建立路徑(pathway)資料表 15
2-3-4統計模型 15
第三章結果 17
3-1 統計學分析結果 17
3-1-1 資料篩選 17
3-2 生物學分析結果 17
3-2-1表現強度變化之基因的分析 17
3-3 KEGG生物路徑資料庫定位 18
3-3-1可信度門檻基因群於KEGG網路中化學基因元素之轉換與分析 18
3-3-2 1.5倍以上變化基因於KEGG網路中化學基因元素之轉換與分析 18
第四章討論 20
4-1 KegArray的使用評測 20
4-2 NGF treated實驗組之基因變化 21

參考文獻

1. Snoep, J.L., From isolation to integration, a systems biology approach for building the Silicon Cell, in Systems Biology, A.L.a.W. H.V., Editor. 2005.
2. Kitano, H., Systems biology: a brief overview. Science, 2002. 295(5560): p. 1662-4.
3. Li, H., Y. Sun, and M. Zhan, Exploring pathways from gene co-expression to network dynamics. Methods Mol Biol, 2009. 541: p. 249-67.
4. Wheelock, C.E., et al., Systems biology approaches and pathway tools for
investigating cardiovascular disease. Mol Biosyst, 2009. 5(6): p. 588-602.
5. Csete, M.E. and J.C. Doyle, Reverse engineering of biological complexity. Science, 2002. 295(5560): p. 1664-9.
6. Baginsky, S., et al., Gene expression analysis, proteomics, and network discovery. Plant Physiol, 2010. 152(2): p. 402-10.
7. Khatri, P. and S. Draghici, Ontological analysis of gene expression data: current tools, limitations, and open problems. Bioinformatics, 2005. 21(18): p. 3587-95.
8. Cho, R.J., et al., Transcriptional regulation and function during the human cell cycle. Nat Genet, 2001. 27(1): p. 48-54.
9. Man, M.Z., X. Wang, and Y. Wang, POWER_SAGE: comparing statistical tests for SAGE experiments. Bioinformatics, 2000. 16(11): p. 953-9.
10. Kanehisa, M., et al., From genomics to chemical genomics: new developments in
KEGG. Nucleic Acids Res, 2006. 34(Database issue): p. D354-7.
11. Ogata, H., et al., KEGG: Kyoto Encyclopedia of Genes and Genomes. Nucleic Acids Res, 1999. 27(1): p. 29-34.
12. Kanehisa, M. and S. Goto, KEGG: kyoto encyclopedia of genes and genomes. Nucleic Acids Res, 2000. 28(1): p. 27-30.
13. Kanehisa, M., et al., KEGG for representation and analysis of molecular networks
involving diseases and drugs. Nucleic Acids Res, 2010. 38(Database issue): p.D355-60.
14. Levi-Montalcini, R., The nerve growth factor: its role in growth, differentiation and function of the sympathetic adrenergic neuron. Prog Brain Res, 1976. 45: p. 235-58.
15. Eggert, A., et al., TrkA signal transduction pathways in neuroblastoma. Med Pediatr Oncol, 2001. 36(1): p. 108-10.
16. Chang, J.H., et al., Persistent TrkA activity is necessary to maintain transcription in
neuronally differentiated PC12 cells. J Biol Chem, 2003. 278(44): p. 42877-85.
17. Yuan, J. and B.A. Yankner, Apoptosis in the nervous system. Nature, 2000. 407(6805): p. 802-9.
18. Sakai, Y., et al., PACAP activates Rac1 and synergizes with NGF to activate ERK1/2,
thereby inducing neurite outgrowth in PC12 cells. Brain Res Mol Brain Res, 2004.
123(1-2): p. 18-26.
19. Lonn, P., et al., BMP enhances transcriptional responses to NGF during PC12 cell
differentiation. Neurochem Res, 2005. 30(6-7): p. 753-65.
20. Vaudry, D., et al., Signaling pathways for PC12 cell differentiation: making the right connections. Science, 2002. 296(5573): p. 1648-9.
21. Tischler, A.S. and L.A. Greene, Nerve growth factor-induced process formation by
cultured rat pheochromocytoma cells. Nature, 1975. 258(5533): p. 341-2.
22. Nankova, B.B., et al., Nicotinic induction of preproenkephalin and tyrosine hydroxylase gene expression in butyrate-differentiated rat PC12 cells: a model for adaptation to gut-derived environmental signals. Pediatr Res, 2003. 53(1): p. 113-8.
23. Mazzio, E., et al., Effect of antioxidants on L-glutamate and
N-methyl-4-phenylpyridinium ion induced-neurotoxicity in PC12 cells. Neurotoxicology, 2001. 22(2): p. 283-8.
24. Crisanti, P., et al., Aspirin prevention of NMDA-induced neuronal death by direct
protein kinase Czeta inhibition. J Neurochem, 2005. 93(6): p. 1587-93.
25. Lee, E., et al., Effects of NMDA receptor inhibition by phencyclidine on the neuronal differentiation of PC12 cells. Neurotoxicology, 2006. 27(4): p. 558-66.
26. Song, Y., et al., Minocycline protects PC12 cells against NMDA-induced injury via
inhibiting 5-lipoxygenase activation. Brain Res, 2006. 1085(1): p. 57-67.
27. Santos, S.D., P.J. Verveer, and P.I. Bastiaens, Growth factor-induced MAPK network topology shapes Erk response determining PC-12 cell fate. Nat Cell Biol, 2007. 9(3): p.324-30.
28. Greenberg, M.E. and E.B. Ziff, Stimulation of 3T3 cells induces transcription of the
c-fos proto-oncogene. Nature, 1984. 311(5985): p. 433-8.
29. Bartel, D.P., et al., Growth factors and membrane depolarization activate distinct
programs of early response gene expression: dissociation of fos and jun induction.
Genes Dev, 1989. 3(3): p. 304-13.
30. Sun, P., et al., Sustained activation of M-Ras induced by nerve growth factor is
essential for neuronal differentiation of PC12 cells. Genes Cells, 2006. 11(9): p.1097-113.
31. Asakura, K., et al., Clioquinol inhibits NGF-induced Trk autophosphorylation and
neurite outgrowth in PC12 cells. Brain Res, 2009. 1301: p. 110-5.
32. Rezaee, F., et al., Neurotrophins regulate bone marrow stromal cell IL-6 expression through the MAPK pathway. PLoS One, 2010. 5(3): p. e9690.

指導教授

凌慶東(Qing-Dong Ling)

審核日期

2010-7-19

推文