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http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/7026完整後設資料紀錄
| DC 欄位 | 值 | 語言 |
|---|---|---|
| dc.contributor.advisor | 李心予(Hsinyu Lee) | |
| dc.contributor.author | Yu-Nung Lin | en |
| dc.contributor.author | 林予農 | zh_TW |
| dc.date.accessioned | 2021-05-17T09:24:24Z | - |
| dc.date.available | 2012-08-22 | |
| dc.date.available | 2021-05-17T09:24:24Z | - |
| dc.date.copyright | 2012-08-22 | |
| dc.date.issued | 2012 | |
| dc.date.submitted | 2012-08-19 | |
| dc.identifier.citation | 1. Aoki J (2004) mechanisms of lysophosphatidic acid production. Seminars in Cell & Developmental Biology 15(5): 477-489
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Journal of the National Cancer Institute 100(22):1630-1642. 40. Lai YJ, Chen CS, Lin WC, & Lin FT (2005) c-Src-mediated phosphorylation of TRIP6 regulates its function in lysophosphatidic acid-induced cell migration. Molecular and Cellular Biology 25(14):5859-5868. 41. Lai YJ, Lin WC, & Lin FT (2007) PTPL1/FAP-1 negatively regulates TRIP6 function in lysophosphatidic acid-induced cell migration. Journal of Biological Chemistry 282(33):24381-24387. 42. Lin FT & Lai YJ (2008) Regulation of the LPA(2) receptor signaling through the carboxyl-terminal tail-mediated protein-protein interactions. Biochimica Et Biophysica Acta-Molecular and Cell Biology of Lipids 1781(9):558-562. 43. Komachi M, et al. (2009) LPA(1) receptors mediate stimulation, whereas LPA(2) receptors mediate inhibition, of migration of pancreatic cancer cells in response to lysophosphatidic acid and malignant ascites. Carcinogenesis 30(3):457-465. 44. Bandoh K, et al. 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Lee CW, Rivera R, Dubin AE, & Chun J (2007) LPA(4)/GPR23 is a lysophosphatidic acid (LPA) receptor utilizing G(s)-, G(q)/G(i)-mediated calcium signaling and G(12/13)-mediated Rho activation. Journal of Biological Chemistry 282(7):4310-4317. 50. Yanagida K, Ishii S, Hamano F, Noguchi K, & Shimizu T (2007) LPA(4)/p2y(9)/GPR23 mediates rho-dependent morphological changes in a rat neuronal cell line. Journal of Biological Chemistry 282(8):5814-5824. 51. Janssens R, Boeynaems JM, Godart M, & Communi D (1997) Cloning of a human heptahelical receptor closely related to the P2Y(5) receptor. Biochemical and Biophysical Research Communications 236(1):106-112. 52. Odowd BF, et al. (1997) Cloning and chromosomal mapping of four putative novel human G-protein-coupled receptor genes. Gene 187(1):75-81. 53. Lee Z, et al. (2008) Role of LPA(4)/p2y9/GPR23 in Negative Regulation of Cell Motility. Molecular Biology of the Cell 19(12):5435-5445. 54. Kotarsky K, et al. (2006) Lysophosphatidic acid binds to and activates GPR92, a G protein-coupled receptor highly expressed in gastrointestinal lymphocytes. Journal of Pharmacology and Experimental Therapeutics 318(2):619-628. 55. Lee CW, Rivera R, Gardell S, Dubin AE, & Chun J (2006) GPR92 as a new G(12/13)- and G(q)-coupled lysophosphatidic acid receptor that increases cAMP, LPA(5). Journal of Biological Chemistry 281(33):23589-23597. 56. Oh DY, et al. (2008) Identification of farnesyl pyrophosphate and N-arachidonylglycine as endogenous ligands for GPR92. Journal of Biological Chemistry 283(30):21054-21064. 57. Yin H, et al. (2009) Lipid G Protein-coupled Receptor Ligand Identification Using beta-Arrestin PathHunter (TM) Assay. Journal of Biological Chemistry 284(18):12328-12338. 58. Williams JR, et al. (2009) Unique Ligand Selectivity of the GPR92/LPA(5) Lysophosphatidate Receptor Indicates Role in Human Platelet Activation. Journal of Biological Chemistry 284(25):17304-17319. 59. Sen S, Smeby RR, & Bumpus FM (1968) Antihypertensice effect of an isolated phospholipid. American Journal of Physiology 214(2):337-41. 60. Tokumura A, Fukuzawa K, & Tsukatani H (1978) Effects of synthetic and natural lysophosphatidic acids on arterial blood-pressure of different animal species. Lipids 13(8):572-574. 61. Anliker B & Chun J (2004) Cell surface receptors in lysophospholipid signaling. Seminars in Cell & Developmental Biology 15(5):457-465. 62. Choi JW, Lee CW, & Chun J (2008) Biological roles of lysophospholipid receptors revealed by genetic null mice: An update. Biochimica Et Biophysica Acta-Molecular and Cell Biology of Lipids 1781(9):531-539. | |
| dc.identifier.uri | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/7026 | - |
| dc.description.abstract | 水解磷酸酯 (lysophosphatidic acid) 是一種結構簡單的水解磷酯 (lysophospholipid)，它與許多生理作用如傷口癒合、癌症惡化、心血管活動、神經調節運作、生殖系統調節、血小板活化與毛髮生長等過程皆密切相關。水解磷酸酯主要經由一具有水解磷酯酶 (lysophospholipase D) 活性的酵素 (autotaxin) 催化磷酯 (phospholipid) 分解而成，並進一步作為膜外訊息傳遞分子，以活化不同受器，如水解磷酸酯受器1-6。為了解不同受器的功能，前人的研究利用催化水解磷酸酯生成酵素 (autotaxin) 基因被抑制的小鼠，分析在水解磷酸酯缺少的情況下小鼠所受到的影響，進而發現由於血管發育缺陷所導致的早期胚胎死亡。然而，在其他研究中，水解磷酸酯受器1-3基因被抑制的小鼠中並沒有類似的症狀出現。本研究探討水解磷酸酯受器4，以期發現其可能活化的下游途徑。藉由斑馬魚平台，在注射抑制基因表現分子而導致水解磷酸酯受器4缺少的早期斑馬魚胚胎中，發現不正常的發育現象。除了可能由血管滲漏與淋巴管回收體液不完全所導致的心臟水腫，也同時觀察到心跳速率與血液流速的明顯降低。另外，體節間縱向血管數目的減少及異常的生長方向，也顯示出血管發育的異常。但是，在運用注射大分子葡聚糖 (dextran, tetramethylrhodamine) 觀察循環系統的結果中，淋巴管的發育並沒有受到明顯影響。總結以上，我們認為在斑馬魚中，水解磷酸酯4有調控血管發育的可能性。 | zh_TW |
| dc.description.abstract | Lysophosphatidic acid, LPA, is a structurally simple lysophospholipid. Derived from phospholipids through autotaxin catalyzation, LPA acts as an extracellular signaling molecule that activates various receptors, LPA1-6. Activation of these receptors induces wound healing, cancer progression, cardiovascular function, nervous system regulation, reproduction, platelet activation, hair growth, etc. To clarify the function of different LPA receptors, several knockout animals have been obtained. While the autotaxin deficient mice expressed the phenotype of embryonic lethality due to vascular defects, none of the single or double deficient LPA1-3 mice expressed similar phenotypes. In this study, I investigate the physiological roles of LPA4, which is structurally distinct from LPA1-3, using zebrafish as a model. LPA4 morpholino was microinjected into one-cell stage zebrafish embryo to knock down the expression level of LPA4 in embryos. In day two, edema around the pericardial region was observed, suggesting a vascular leakage or failure of lymphatic vessels to absorb body fluids in the LPA4 deficient embryos, which was similar to the result of a previous study where LPA1 was found to be essential for lymphatic vessel development in zebrafish. In addition, a significant decrease in heart rate and blood flow was observed in some individuals. Furthermore, the number of intersegmental vessels decreased, suggesting abnormal blood vessel development. However, the dextran uptake was not affected in the LPA4 knock down embryos, suggesting that the development of lymphatic vessels was normal. We conclude that LPA4 may regulate the vascular development in zebrafish. | en |
| dc.description.provenance | Made available in DSpace on 2021-05-17T09:24:24Z (GMT). No. of bitstreams: 1 ntu-101-R99b41010-1.pdf: 20128456 bytes, checksum: 4994c7b041d379320ef3e6e3fc01ecee (MD5) Previous issue date: 2012 | en |
| dc.description.tableofcontents | 口試委員會審定書 i
致謝 ii 摘要 iii ABSTRACT iv CATALOG vi INTRODUCTION 1 Metabolism of LPA 1 LPA receptors 2 Functions of LPA receptors 3 RATIONALE 5 MODEL 6 MATERIALS AND METHODS 7 Maintenance of zebrafish 7 The expression profiling of LPA4 in zebrafish by RT-PCR 7 Microinjection procedures 8 Design of morpholino oligonucleotides 9 Edema examination 9 Rhodamine-dextran injection 10 Microscopic analysis and live imaging 10 RESULTS 11 Expression profile of LPA4 in zebrafish 11 Edema under zebrafish LPA4 morpholino microinjection 11 Abnormal heartbeat and circulation in LPA4 deficient zebrafish 12 Abnormal vascular pattern in LPA4 knock down zebrafish 13 Lymphatic development in LPA4 deficient zebrafish 13 DISCUSSION 15 REFERENCES 18 FIGURES 28 Fig. 1 Expression profile of LPA4 in zebrafish 28 Fig. 2 Edema under zebrafish LPA4 morpholino microinjection 29 Fig. 3 Edema reamain under homeostasis condition 30 Fig. 4 Heartbeat and blood flow decrease under zebrafish LPA4 morpholino microinjection 31 Fig. 5 Normal developed vascular pattern 32 Fig. 6 Abnormal of vascular pattern in knock down LPA4 zebrafish 33 Fig. 7 Absence of intersegmental vessels in knock down LPA4 zebrafish 34 Fig. 8 Lymphatic development under zebrafish LPA4 morpholino microinjection 35 TABLES 36 Table 1 Analysis of pericardial abnormality under knock down of LPA4 in zebrafish 36 Table 2 Analysis of blood circulation slowdown under knock down of LPA4 in zebrafish 37 Table 3 Analysis of vascular defects under knock down of LPA4 in zebrafish 38 | |
| dc.language.iso | en | |
| dc.title | 斑馬魚水解磷酸酯受器4功能之研究 | zh_TW |
| dc.title | The Investigation of LPA Receptor 4 Functions in Zebrafish | en |
| dc.type | Thesis | |
| dc.date.schoolyear | 100-2 | |
| dc.description.degree | 碩士 | |
| dc.contributor.oralexamcommittee | 張百恩(Bei-En Chang),蕭崇德(Chung-Der Hsiao) | |
| dc.subject.keyword | 水解磷酸酯,水解磷酸酯受器,血管,發育,斑馬魚, | zh_TW |
| dc.subject.keyword | lysophosphatidic acid,G-protein coupled receptor,blood vessel,development,zebrafish, | en |
| dc.relation.page | 38 | |
| dc.rights.note | 同意授權(全球公開) | |
| dc.date.accepted | 2012-08-19 | |
| dc.contributor.author-college | 生命科學院 | zh_TW |
| dc.contributor.author-dept | 動物學研究所 | zh_TW |
| 顯示於系所單位： | 動物學研究所 | |
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