請用此 Handle URI 來引用此文件：
http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/77505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 | Pei-Yun Chuang | en |
| dc.contributor.author | 莊珮筠 | zh_TW |
| dc.date.accessioned | 2021-07-10T22:05:54Z | - |
| dc.date.available | 2021-07-10T22:05:54Z | - |
| dc.date.copyright | 2018-08-23 | |
| dc.date.issued | 2018 | |
| dc.date.submitted | 2018-08-15 | |
| dc.identifier.citation | 1. Kewley, R.J., M.L. Whitelaw, and A. Chapman-Smith, The mammalian basic helix–loop–helix/PAS family of transcriptional regulators. The International Journal of Biochemistry & Cell Biology, 2004. 36(2): p. 189-204.
2. Bersten, D.C., et al., bHLH-PAS proteins in cancer. Nat Rev Cancer, 2013. 13(12): p. 827-41. 3. Ellen C. Henry, T.A.G., Transformation of the arylhydrocarbon receptor to a DNA-binding form is accompanied by release of the 90 kDa heat-shock protein and increased afinityfor2,3,7,8-tetrachlorodibenzo-p-dioxin. Biochem, 1993. 249: p. 95-101. 4. Denis, M., et al., Association of the dioxin receptor with the Mr 90,000 heat shock protein- A structural kinship with the glucocorticoid receptor. Biomedical and Biophysical Research Communications, 1988. 155(2): p. 801-807. 5. Carver, L.A. and C.A. Bradfield, Ligand-dependent interaction of the aryl hydrocarbon receptor with a novel immunophilin homolog in vivo. J Biol Chem, 1997. 272(17): p. 11452-6. 6. Grenert, J.P., et al., The amino-terminal domain of heat shock protein 90 (hsp90) that binds geldanamycin is an ATP/ADP switch domain that regulates hsp90 conformation. J Biol Chem, 1997. 272(38): p. 23843-50. 7. Dong, B., et al., FRET analysis of protein tyrosine kinase c-Src activation mediated via aryl hydrocarbon receptor. Biochim Biophys Acta, 2011. 1810(4): p. 427-31. 8. Murray Whitelaw, I.P., Anna Wilhelmsson, Jan-ake Gustafsson and Lorenz Poellinger, Ligand-Dependent Recruitment of the Arnt Coregulator DeterminesDNA Recognition by the Dioxin Receptor. Mol. Cell. Bio, 1993. 13: p. 2504-2514. 9. Scott E. Heid, R.S.P., and Hollie I. Swanson, Role of Heat Shock Protein 90 Dissociation in Mediating Agonist-Induced Activation of the Aryl Hydrocarbon Receptor. Mol. Pharmacol., 1999. 57: p. 82–92. 10. James P. Whitlock, J., Induction of cytochrome 450 1a1. Annu. Rev. Pharmacol. Toxicol., 1991. 39: p. 103–25. 11. Daniel W. Nebert, A.L.R., Matthew Z. Dieter, Willy A. Solis, Yi Yang and Timothy P. Dalton, Role of the Aromatic Hydrocarbon Receptor and [Ah] Gene Battery in the Oxidative Stress Response, Cell Cycle Control, and Apoptosis. Biochemical Pharmacology, 2000. 59: p. 65–85. 12. Swanson, H.I., DNA binding and protein interactions of the AHR/ARNT heterodimer that facilitate gene activation. Chemico-Biological Interactions, 2002. 141: p. 63–76. 13. Jin, D.Q., et al., 2,3,7,8-Tetrachlorodibenzo-p-dioxin inhibits cell proliferation through arylhydrocarbon receptor-mediated G1 arrest in SK-N-SH human neuronal cells. Neurosci Lett, 2004. 363(1): p. 69-72. 14. Marlowe, J.L., et al., The aryl hydrocarbon receptor displaces p300 from E2F-dependent promoters and represses S phase-specific gene expression. J Biol Chem, 2004. 279(28): p. 29013-22. 15. Jennifer L. Marlowe, Y.F., Xiaoqing Chang, Li Peng, Erik S. Knudsen, Ying Xia, and Alvaro Puga, The Aryl Hydrocarbon Receptor Binds to E2F1 and Inhibits E2F1-induced Apoptosis. Molecular Biology of the Cell, 2008. 19: p. 3263–3271. 16. Yuichi Watabe, N.N., Masakatsu Tezuka, and Shigeki Shimba, Aryl Hydrocarbon Receptor Functions as a Potent Coactivator of E2F1- Dependent Trascription Activity. Biol. Pharm. Bull., 2010. 33(3): p. 389—397. 17. Quintana, F.J., Regulation of central nervous system autoimmunity by the aryl hydrocarbon receptor. Semin Immunopathol, 2013. 35(6): p. 627-35. 18. Murray, I.A., A.D. Patterson, and G.H. Perdew, Aryl hydrocarbon receptor ligands in cancer: friend and foe. Nat Rev Cancer, 2014. 14(12): p. 801-14. 19. Nguyen, N.T., et al., Aryl hydrocarbon receptor and kynurenine: recent advances in autoimmune disease research. Front Immunol, 2014. 5: p. 551. 20. Prendergast, G.C., et al., IDO2 in Immunomodulation and Autoimmune Disease. Front Immunol, 2014. 5: p. 585. 21. Wu, P.-Y., et al., Aryl Hydrocarbon Receptor Downregulates MYCN Expression and Promotes Cell Differentiation of Neuroblastoma. PLoS ONE, 2014. 9(2): p. e88795. 22. Fernandez-Salguero, P., et al., Immune system impairment and hepatic fibrosis in mice lacking the dioxin-binding Ah receptor. Science, 1995. 268(5211): p. 722-6. 23. Schmidt, J.V., et al., Characterization of a murine Ahr null allele: involvement of the Ah receptor in hepatic growth and development. Proc Natl Acad Sci U S A, 1996. 93(13): p. 6731-6. 24. Mimura, J., et al., Loss of teratogenic response to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) in mice lacking the Ah (dioxin) receptor. Genes Cells, 1997. 2(10): p. 645-54. 25. Benedict, J.C., et al., Physiological role of the aryl hydrocarbon receptor in mouse ovary development. Toxicol Sci, 2000. 56(2): p. 382-8. 26. Billiard, S.M., et al., The role of the aryl hydrocarbon receptor pathway in mediating synergistic developmental toxicity of polycyclic aromatic hydrocarbons to zebrafish. Toxicol Sci, 2006. 92(2): p. 526-36. 27. Goodale, B.C., et al., AHR2 mutant reveals functional diversity of aryl hydrocarbon receptors in zebrafish. PLoS One, 2012. 7(1): p. e29346. 28. Chevallier, A., et al., Oculomotor Deficits in Aryl Hydrocarbon Receptor Null Mouse. PLoS ONE, 2013. 8(1): p. e53520. 29. Wang, Q., et al., Disruption of aryl hydrocarbon receptor homeostatic levels during embryonic stem cell differentiation alters expression of homeobox transcription factors that control cardiomyogenesis. Environ Health Perspect, 2013. 121(11-12): p. 1334-43. 30. Aluru, N., M.J. Jenny, and M.E. Hahn, Knockdown of a zebrafish aryl hydrocarbon receptor repressor (AHRRa) affects expression of genes related to photoreceptor development and hematopoiesis. Toxicol Sci, 2014. 139(2): p. 381-95. 31. Latchney, S.E., et al., Deletion or activation of the aryl hydrocarbon receptor alters adult hippocampal neurogenesis and contextual fear memory. J Neurochem, 2013. 125(3): p. 430-45. 32. Xie, H.Q., et al., AhR-mediated effects of dioxin on neuronal acetylcholinesterase expression in vitro. Environ Health Perspect, 2013. 121(5): p. 613-8. 33. Kim, S.Y., et al., Deletion of aryl hydrocarbon receptor AHR in mice leads to subretinal accumulation of microglia and RPE atrophy. Invest Ophthalmol Vis Sci, 2014. 55(9): p. 6031-40. 34. Richard B. Emmons1, D.D., Patricia A. Estes2, Paula Kiefel1, Jack T. Mosher2, Margaret Sonnenfeld2, Mary P. Ward2, Ian Duncan1 and Stephen T. Crews2,, The Spineless-Aristapedia and Tango bHLH-PAS proteins interact to control antennal and tarsal development in Drosophila. Development, 1999. 126: p. 3937-3945. 35. Sandra L. Petersen, M.A.C., Sharon A. Marconi, Clifford D. Carpenter, Laura S. Lubbers, and Michael D. Mcabee, Distribution of mRNAs Encoding the Arylhydrocarbon Receptor, Arylhydrocarbon Receptor Nuclear Translocator, and Arylhydrocarbon Receptor Nuclear Translocator-2 in the Rat Brain and Brainstem. J Comp Neurol. 2000. 427: p. 428–439. 36. Hahn, M.E., Aryl hydrocarbon receptors: diversity and evolution. Chemico-Biological Interactions, 2002. 141: p. 131-160. 37. Huang, X., J.A. Powell-Coffman, and Y. Jin, The AHR-1 aryl hydrocarbon receptor and its co-factor the AHA-1 aryl hydrocarbon receptor nuclear translocator specify GABAergic neuron cell fate in C. elegans. Development, 2004. 131(4): p. 819-28. 38. Kim, M.D., L.Y. Jan, and Y.N. Jan, The bHLH-PAS protein Spineless is necessary for the diversification of dendrite morphology of Drosophila dendritic arborization neurons. Genes Dev, 2006. 20(20): p. 2806-19. 39. Collins, L.L., et al., 2,3,7,8-Tetracholorodibenzo-p-dioxin exposure disrupts granule neuron precursor maturation in the developing mouse cerebellum. Toxicol Sci, 2008. 103(1): p. 125-36. 40. Nguyen, L.P. and C.A. Bradfield, The Search for Endogenous Activators of the Aryl Hydrocarbon Receptor. Chemical Research in Toxicology, 2008. 21(1): p. 102-116. 41. Ociepa-Zawal, M., et al., The effect of indole-3-carbinol on the expression of CYP1A1, CYP1B1 and AhR genes and proliferation of MCF-7 cells. Acta Biochim Pol, 2007. 54(1): p. 113-7. 42. Gillam, E.M., et al., Oxidation of indole by cytochrome P450 enzymes. Biochemistry, 2000. 39(45): p. 13817-24. 43. Opitz, C.A., et al., An endogenous tumour-promoting ligand of the human aryl hydrocarbon receptor. Nature, 2011. 478(7368): p. 197-203. 44. Takenaka, M.C., S. Robson, and F.J. Quintana, Regulation of the T Cell Response by CD39. Trends in Immunology, 2016. 37(7): p. 427-439. 45. Gabriely, G., et al., Role of AHR and HIF-1alpha in Glioblastoma Metabolism. Trends Endocrinol Metab, 2017. 28(6): p. 428-436. 46. Karchner, S.I., D.G. Franks, and M.E. Hahn, AHR1B, a new functional aryl hydrocarbon receptor in zebrafish: tandem arrangement of ahr1b and ahr2 genes. Biochem J, 2005. 392(Pt 1): p. 153-61. 47. Fraccalvieri, D., et al., Comparative analysis of homology models of the AH receptor ligand binding domain: verification of structure-function predictions by site-directed mutagenesis of a nonfunctional receptor. Biochemistry, 2013. 52(4): p. 714-25. 48. Kubota, A., et al., Role of zebrafish cytochrome P450 CYP1C genes in the reduced mesencephalic vein blood flow caused by activation of AHR2. Toxicol Appl Pharmacol, 2011. 253(3): p. 244-52. 49. Bugel, S.M., L.A. White, and K.R. Cooper, Inhibition of vitellogenin gene induction by 2,3,7,8-tetrachlorodibenzo-p-dioxin is mediated by aryl hydrocarbon receptor 2 (AHR2) in zebrafish (Danio rerio). Aquat Toxicol, 2013. 126: p. 1-8. 50. Wang, W.D., et al., Aryl hydrocarbon receptor 2 mediates the toxicity of Paclobutrazol on the digestive system of zebrafish embryos. Aquat Toxicol, 2015. 159: p. 13-22. 51. Incardona, J.P., et al., Aryl Hydrocarbon Receptor–Independent Toxicity of Weathered Crude Oil during Fish Development. Environmental Health Perspectives, 2005. 113(12): p. 1755-1762. 52. Incardona, J.P., et al., Developmental toxicity of 4-ring polycyclic aromatic hydrocarbons in zebrafish is differentially dependent on AH receptor isoforms and hepatic cytochrome P4501A metabolism. Toxicol Appl Pharmacol, 2006. 217(3): p. 308-21. 53. Jonsson, M.E., et al., Role of AHR2 in the expression of novel cytochrome P450 1 family genes, cell cycle genes, and morphological defects in developing zebra fish exposed to 3,3',4,4',5-pentachlorobiphenyl or 2,3,7,8-tetrachlorodibenzo-p-dioxin. Toxicol Sci, 2007. 100(1): p. 180-93. 54. Lanham, K.A., et al., A dominant negative zebrafish Ahr2 partially protects developing zebrafish from dioxin toxicity. PLoS One, 2011. 6(12): p. e28020. 55. Van Tiem, L.A. and R.T. Di Giulio, AHR2 knockdown prevents PAH-mediated cardiac toxicity and XRE- and ARE-associated gene induction in zebrafish (Danio rerio). Toxicol Appl Pharmacol, 2011. 254(3): p. 280-7. 56. Timme-Laragy, A.R., S.I. Karchner, and M.E. Hahn, Gene knockdown by morpholino-modified oligonucleotides in the zebrafish (Danio rerio) model: applications for developmental toxicology. Methods Mol Biol, 2012. 889: p. 51-71. 57. Wincent, E., et al., Biological effects of 6-formylindolo[3,2-b]carbazole (FICZ) in vivo are enhanced by loss of CYP1A function in an Ahr2-dependent manner. Biochem Pharmacol, 2016. 110-111: p. 117-29. 58. Eric A. Anderson, M.E.H., Warren Heideman, Richard E. Peterson, and Robert L. Tanguay, The Zebrafish (Danio rerio) Aryl Hydrocarbon Receptor Type 1 Is a Novel Vertebrate Receptor. Mol Pharmacol, 2002. 62: p. 234–249. 59. Garner, L.V., D.R. Brown, and R.T. Di Giulio, Knockdown of AHR1A but not AHR1B exacerbates PAH and PCB-126 toxicity in zebrafish (Danio rerio) embryos. Aquat Toxicol, 2013. 142-143: p. 336-46. 60. Eric A. Andreasen, J.M.S., Robert L. Tanguay, John J. Stegeman, Warren Heideman, Richard E. Peterson, Tissue-Specific Expression of AHR2, ARNT2, and CYP1A in Zebrafish Embryos and Larvae: Effects of Developmental Stage and 2,3,7,8-Tetrachlorodibenzo-p-dioxin Exposure. Toxicol Sci. 2002. 68: p. 403–419. 61. Wang, B.J., et al., Establishment of a cell-free bioassay for detecting dioxin-like compounds. Toxicol Mech Methods, 2013. 23(6): p. 464-70. 62. R. C. Melcangi, V.M., I. Cavarretta, L. Martini, F. Piva, Age-induced decrease of glycoprotein PO and myelin basic protein gene expression in the rat sciatic nerve. Repair by steroid derivatives. Neuroscience, 1998. 85(2): p. 569–578. 63. Higashi, T., et al., Studies on neurosteroids XXIII. Analysis of tetrahydrocorticosterone isomers in the brain of rats exposed to immobilization using LC-MS. Steroids, 2007. 72(13): p. 865-74. 64. Melcangi, R.C., L.M. Garcia-Segura, and A.G. Mensah-Nyagan, Neuroactive steroids: state of the art and new perspectives. Cell Mol Life Sci, 2008. 65(5): p. 777-97. 65. Pelletier, G., Steroidogenic Enzymes in the Brain: Morphological Aspects. 2010. 181: p. 193-207. 66. Diotel, N., et al., The brain of teleost fish, a source, and a target of sexual steroids. Front Neurosci, 2011. 5: p. 137. 67. Kelleher, M.A., J.J. Hirst, and H.K. Palliser, Changes in neuroactive steroid concentrations after preterm delivery in the Guinea pig. Reprod Sci, 2013. 20(11): p. 1365-75. 68. Brunton, P.J., J.A. Russell, and J.J. Hirst, Allopregnanolone in the brain: protecting pregnancy and birth outcomes. Prog Neurobiol, 2014. 113: p. 106-36. 69. Jenkins, S.I., et al., Identifying the cellular targets of drug action in the central nervous system following corticosteroid therapy. ACS Chem Neurosci, 2014. 5(1): p. 51-63. 70. Melcangi, R.C., S. Giatti, and L.M. Garcia-Segura, Levels and actions of neuroactive steroids in the nervous system under physiological and pathological conditions: Sex-specific features. Neurosci Biobehav Rev, 2015. 71. R. C. Melcangi, F.C., M. Ballabio, A. Poletti, P. Castano and L. Martini, Testosterone 5 alpha-reductase activity in the rat brain is highly concentrated in white matter structures and in purified myelin sheaths of axons. Steroid Biochem., 1988. 31: p. 173-179. 72. F. Celotti, R.C.M., P. Negri-cesIand A. Polett Testosterine metabolism in BRAIN cells and membranes. Steroid Biochem. Molec. Biol., 1991. 40: p. 673-678. 73. Angelo Poletti, F.C., Cristiano Rumio, Monica Rabuffetti, Luciano Martini, Identification of type 1 5h-reductase in myelin membranes of male and female rat brain. Molecular and Cellular Endocrinology, 1997. 129: p. 181–190. 74. Tsuruo, Y., Topography and function of androgen-metabolizing enzymes in the central nervous system. Anatomical Science International, 2005. 80: p. 1-11. 75. Saalmann, Y.B., et al., Cellular distribution of the GABAA receptor-modulating 3alpha-hydroxy, 5alpha-reduced pregnane steroids in the adult rat brain. J Neuroendocrinol, 2007. 19(4): p. 272-84. 76. Pesaresi, M., et al., Dihydroprogesterone increases the gene expression of myelin basic protein in spinal cord of diabetic rats. J Mol Neurosci, 2010. 42(2): p. 135-9. 77. Azzouni, F., et al., The 5 alpha-reductase isozyme family: a review of basic biology and their role in human diseases. Adv Urol, 2012. 2012: p. 530121. 78. Campagnoni, J.M.V.a.A.T., Translational Regulation by Steroids. J Biol Chem , 1990. 265(25): p. 20314-20320. 79. Raphael, A.R. and W.S. Talbot, New insights into signaling during myelination in zebrafish. Curr Top Dev Biol, 2011. 97: p. 1-19. 80. Crawford, A.H., C. Chambers, and R.J. Franklin, Remyelination: the true regeneration of the central nervous system. J Comp Pathol, 2013. 149(2-3): p. 242-54. 81. Barateiro, A. and A. Fernandes, Temporal oligodendrocyte lineage progression: in vitro models of proliferation, differentiation and myelination. Biochim Biophys Acta, 2014. 1843(9): p. 1917-29. 82. From, R., et al., Oligodendrogenesis and myelinogenesis during postnatal development effect of glatiramer acetate. Glia, 2014. 62(4): p. 649-65. 83. Ackerman, S.D. and K.R. Monk, The scales and tales of myelination: using zebrafish and mouse to study myelinating glia. Brain Res, 2015. 84. Lyons, D.A. and W.S. Talbot, Glial cell development and function in zebrafish. Cold Spring Harb Perspect Biol, 2015. 7(2): p. a020586. 85. Ravanelli, A.M. and B. Appel, Motor neurons and oligodendrocytes arise from distinct cell lineages by progenitor recruitment. Genes Dev, 2015. 29(23): p. 2504-15. 86. Czopka, T., Insights into mechanisms of central nervous system myelination using zebrafish. Glia, 2016. 64(3): p. 333-49. 87. Marinelli, C., et al., Systematic Review of Pharmacological Properties of the Oligodendrocyte Lineage. Front Cell Neurosci, 2016. 10: p. 27. 88. Wang, B.J., et al., Establishment of a bioluminescence-based bioassay for the detection of dioxin-like compounds. Toxicol Mech Methods, 2013. 23(4): p. 247-54. 89. Cheung, Y.T., et al., Effects of all-trans-retinoic acid on human SH-SY5Y neuroblastoma as in vitro model in neurotoxicity research. Neurotoxicology, 2009. 30(1): p. 127-35. 90. Sato, T., M. Takahoko, and H. Okamoto, HuC:Kaede, a useful tool to label neural morphologies in networks in vivo. Genesis, 2006. 44(3): p. 136-42. 91. St John, J.A. and B. Key, HuC-eGFP mosaic labelling of neurons in zebrafish enables in vivo live cell imaging of growth cones. J Mol Histol, 2012. 43(6): p. 615-23. 92. Charles B. Kimmel, W.W.B., Seth R. Kimmel, Bonnie Ullmann, and T.F. Schilling, Stages of embryonic development of the zebrafish. Dev Dyn, 1995. 203: p. 255-310. 93. Wang, W.D., et al., Phenylthiourea as a weak activator of aryl hydrocarbon receptor inhibiting 2,3,7,8-tetrachlorodibenzo-p-dioxin-induced CYP1A1 transcription in zebrafish embryo. Biochem Pharmacol, 2004. 68(1): p. 63-71. 94. Nuti, R., et al., Ligand binding and functional selectivity of L-tryptophan metabolites at the mouse aryl hydrocarbon receptor (mAhR). J Chem Inf Model, 2014. 54(12): p. 3373-83. 95. Togo Ikuta, H.E., Taro Tachibana, Yoshihiro Yoneda, and Kaname Kawajiri, Nuclear Localization and Export Signals of the Human Aryl Hydrocarbon Receptor. J Bio Chem, 1998. 273(January 30): p. 2895–2904. 96. M. S. Denison, S.H.-P., The Ah Receptor: A Regulator of the Biochemical and Toxicological Actions of Structurally Diverse Chemicals. Bull. Environ. Contam. Toxicol., 1998(61): p. 557-568. 97. Scott R. Nagy, G.L., Kit S. Lam, and Michael S. Denison, Identification of Novel Ah Receptor Agonists Using a High-Throughput Green Fluorescent Protein-Based Recombinant Cell Bioassay. Biochemistry, 2002. 41: p. 861-868. 98. Huang, T.C., et al., Silencing of miR-124 induces neuroblastoma SK-N-SH cell differentiation, cell cycle arrest and apoptosis through promoting AHR. FEBS Lett, 2011. 585(22): p. 3582-6. 99. Janardhanan, R., N.L. Banik, and S.K. Ray, N-Myc down regulation induced differentiation, early cell cycle exit, and apoptosis in human malignant neuroblastoma cells having wild type or mutant p53. Biochem Pharmacol, 2009. 78(9): p. 1105-14. 100. L. A. Benjamin, R.C.M., and D. A. Hart, Effect of retinoic acid on human neuroblastoma: Correlation between morphological differentiation and changes in plasminogen activator and inhibitor activity. cancer chemother pharmacol, 1989. 25: p. 25-31. 101. Fernandez, M., et al., A single prenatal exposure to the endocrine disruptor 2,3,7,8-tetrachlorodibenzo-p-dioxin alters developmental myelination and remyelination potential in the rat brain. J Neurochem, 2010. 115(4): p. 897-909. 102. Duarte, J.H., et al., Differential influences of the aryl hydrocarbon receptor on Th17 mediated responses in vitro and in vivo. PLoS One, 2013. 8(11): p. e79819. 103. Rouse, M., et al., Indoles mitigate the development of experimental autoimmune encephalomyelitis by induction of reciprocal differentiation of regulatory T cells and Th17 cells. Br J Pharmacol, 2013. 169(6): p. 1305-21. 104. Yang, E.J., et al., Immunomodulation By Subchronic Low Dose 2,3,7,8-Tetrachlorodibenzo-p-Dioxin in Experimental Autoimmune Encephalomyelitis in the Absence of Pertussis Toxin. Toxicol Sci, 2016. 151(1): p. 35-43. 105. Juricek, L., et al., AhR-deficiency as a cause of demyelinating disease and inflammation. Sci Rep, 2017. 7(1): p. 9794. 106. Shackleford, G., et al., Involvement of Aryl hydrocarbon receptor in myelination and in human nerve sheath tumorigenesis. Proc Natl Acad Sci U S A, 2018. 115(6): p. E1319-E1328. 107. Zhao, T., et al., Dopaminergic neuronal loss and dopamine-dependent locomotor defects in Fbxo7-deficient zebrafish. PLoS One, 2012. 7(11): p. e48911. 108. Fang, Y., et al., A novel model of demyelination and remyelination in a GFP-transgenic zebrafish. Biol Open, 2014. 4(1): p. 62-8. | |
| dc.identifier.uri | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/77505 | - |
| dc.description.abstract | 芳香烴受器 (Aryl hydrocarbon receptor, AHR) 為須經配體 (ligand) 活化的轉錄因子。當 AHR 在細胞質與其外源性配體，如戴奧辛結合時，活化的 AHR 會入核與目標基因結合，並開啟轉錄與轉譯，進而影響許多生理功能如胚胎發育、癌症生成及發炎反應等。然而，關於 AHR 內生性配體之相關研究至今仍不完整。本實驗室利用先前建立的戴奧辛偵測系統在斑馬魚胚胎初萃物中，找到了新的AHR之內生性配體—四氫皮質酮 (tetrahydrocorticosterone, THB)，並發現其中的 5β-THB 可透過活化 AHR 調控斑馬魚的神經分化。然而，同為此受器內生性配體的 5α-THB 是否也透過 AHR 調控特定生理反應仍有待探討，因此，本研究的實驗目標為了解 5α-THB 在 AHR 所影響的生理功能中所扮演的角色。實驗顯示 THB 會活化 AHR，使之入核並調控下游目標基因 Cyp1a1 的表現。先前的研究中已證實 AHR 大量表達會導致神經纖維母細胞瘤細胞 (neuroblastoma) 分化；本研究結果顯示 5α-THB 也具有促進此細胞神經分化的能力。在斑馬魚實驗中，5α/5β-THB 可透過活化 AHR 刺激 zCyp1a 的表現，也對髓鞘相關基因 zSox10、zMbp 有正向調控的作用，且更進一步地影響斑馬魚的泳動能力。綜合以上結果，我們認為 AHR 內生性配體—5α/5β-THB 在斑馬魚的神經分化中扮演了重要角色。 | zh_TW |
| dc.description.abstract | Aryl hydrocarbon receptor (AHR) is a cytosolic ligand-activated transcriptional factor. Once binding to xenobiotic toxic chemicals such as dioxin, AHR triggers downstream signaling and regulates a variety of physiological functions which include embryogenesis, tumorigenesis, and inflammation. However, the characteristic of endogenous AHR ligands remains elusive. In our previous study, tetrahydrocorticosterone (THB) was identified as a potential AHR ligand in zebrafish embryos using a well-established cell-free bioassay for dioxin-like compounds. We also demonstrated that one of the THB, 5β-THB, plays a critical role in neural differentiation in zebrafish. Nevertheless, the role of 5α-THB, a cis-trans isomer of 5β-THB, has not been illustrated. The aim of this study is to investigate the effects of 5α-THB in AHR activation and clarify its physiological functions. Similar to our previous results, 5α-THB was found to induce nucleus translocation of AHR, which subsequently up-regulated the mRNA expression of cytochrome P450 1A1 (CYP1A1) in AHR-overexpressing cells. Besides, 5α-THB promoted neuronal differentiation of neuroblastoma (NB) cells, suggesting that activation of AHR by 5α-THB leads to NB differentiation. Furthermore, 5α/5β-THB both enhanced the expressions of zCyp1a, myelin-associated protein myelin basic protein (zMbp), and sex determining region Y- box 10 (zSox10), and improved the mobility of zebrafish larvae via the Ahr2 pathway. In conclusion, the results in this study suggested that endogenous AHR ligands 5α/5β-THB play critical roles during neural development of zebrafish. | en |
| dc.description.provenance | Made available in DSpace on 2021-07-10T22:05:54Z (GMT). No. of bitstreams: 1 ntu-107-R05b21009-1.pdf: 10443191 bytes, checksum: 8511c33f8f5fe3b5d28ce679d255ed9c (MD5) Previous issue date: 2018 | en |
| dc.description.tableofcontents | 口試委員審定書………………………………………………………………………i
誌謝……………………………………………………………………………………ii 中文摘要………………………………………………………………………………iii Abstract………………………………………………………………………………iv Contents………………………………………………………………………………v 1 Introduction…………………………………………………………………………1 1.1 Aryl Hydrocarbon Receptor (AHR)…………………………………………1 1.2 The physiological roles of AHR………………………………………………1 1.3 The endogenous ligands of AHR……………………………………………2 1.4 Functional characterization between Ahrs in zebrafish…………………………3 1.5 Tetrahydrocorticosterone (THB) and central nervous system…………………3 1.6 The development of myelinating glial cells in zebrafish………………………4 2 Aim…………………………………………………………………………………5 3 Materials and Methods……………………………………………………………5 3.1 Cell culture……………………………………………………………………5 3.2 Chemical reagent………………………………………………………………5 3.3 Cell-free dioxin assay……………………………………………………………6 3.4 High-performance liquid chromatography (HPLC)…………………………6 3.5 LC-ESI-MS………………………………………………………………………7 3.6 Neuroblastoma differentiation assay……………………………………………7 3.7 Zebrafish maintenance, embryos collection, and embryo crude extraction………8 3.8 Gene knockdown by antisense morpholino injection……………………………8 3.9 Chemical treatment in Zebrafish…………………………………………………9 3.10 mRNA extraction………………………………………………………………9 3.11 Reverse-transcription and quantitative real-time PCR…………………………9 3.12 Western Blot……………………………………………………………………11 3.13 Locomotion test and analysis…………………………………………………12 3.14 Fluorescent imaging and analysis……………………………………………12 3.15 Statistical analysis……………………………………………………………13 4 Results………………………………………………………………………………14 4.1 Identification of novel endogenous ligand from zebrafish crude extraction through cell-free dioxin bioassay……………………………………………………14 4.2 5α- and 5β-THB are novel AHR endogenous ligands…………………………15 4.3 5α/5β-THB both have the potential to induce neuronal differentiation…………16 4.4 5α/5β-THB-activated AHR signaling pathway is Ahr2-dependent in zebrafish 16 4.5 The effects of 5α/5β-THB are involved in early neurogenesis…………………17 4.6 5α/5β-THB facilitate the development of myelinating glia via Ahr2-dependent pathway……………………………………………………………………………17 4.7 5α/5β-THB improve the mobility of Ahr2-deficient zebrafish larvae…………18 5 Conclusions and Discussions……………………………………………………19 6 Reference…………………………………………………………………………23 7 Figures………………………………………………………………………………36 Figure 1. Experimental processes to obtain AHR endogenous ligands, from zebrafish crude extract to identification of 5α/5β-THB…………………………………36 Figure 2. 5α/5β-THB-induced nuclear translocation of AHR………………………39 Figure 3. 5α/5β-THB stimulate AHR-target gene expression in AAPA cells………41 Figure 4. 5α/5β-THB-triggered neuroblastoma cells differentiation………………42 Figure 5. 5α/5β-THB stimulate AHR-target gene expression in zebrafish…………44 Figure 6. 5α/5β-THB regulate Ahr2 downstream signaling pathway………………45 Figure 7. 5α/5β-THB are involved in early neurogenesis…………………………47 Figure 8. 5α/5β-THB regulate early development of myelinating glia via an Ahr2-dependent pathway…………………………………………………………………48 Figure 9. 5α/5β-THB involve in the late development of myelinating glia via an Ahr2-dependent pathway…………………………………………………………50 Figure 10. 5α- and 5β-THB improved the mobility of zebrafish larvae……………52 Figure 11. 5α/5β-THB were identified as novel AHR endogenous ligands and were found to regulate neural development via promoting myelination of glial cells……………………54 8 Table…………………………………………………………………………………55 9 Supplementary data………………………………………………………………57 | |
| dc.language.iso | zh-TW | |
| dc.subject | 芳香烴接受器 | zh_TW |
| dc.subject | 芳香烴接受器配體 | zh_TW |
| dc.subject | 神經分化 | zh_TW |
| dc.subject | 斑馬魚 | zh_TW |
| dc.subject | neuronal differentiation | en |
| dc.subject | AHR | en |
| dc.subject | AHR ligand | en |
| dc.subject | neuronal differentiation | en |
| dc.subject | Ahr2 | en |
| dc.subject | zebrafish | en |
| dc.subject | AHR | en |
| dc.subject | AHR ligand | en |
| dc.subject | Ahr2 | en |
| dc.subject | zebrafish | en |
| dc.title | 芳香烴接受器之內生性配體於神經發育之角色 | zh_TW |
| dc.title | Investigation of the Roles of Novel Endogenous Ligands of Aryl Hydrocarbon Receptor in Neural Development in Zebrafish | en |
| dc.type | Thesis | |
| dc.date.schoolyear | 106-2 | |
| dc.description.degree | 碩士 | |
| dc.contributor.oralexamcommittee | 蕭崇德(Chung-Der Hsiao),陳志成(Chih-Cheng Chen),廖永豐(Yung-Feng Liao) | |
| dc.subject.keyword | 芳香烴接受器,芳香烴接受器配體,神經分化,斑馬魚, | zh_TW |
| dc.subject.keyword | AHR,AHR ligand,neuronal differentiation,Ahr2,zebrafish, | en |
| dc.relation.page | 57 | |
| dc.identifier.doi | 10.6342/NTU201803430 | |
| dc.rights.note | 未授權 | |
| dc.date.accepted | 2018-08-15 | |
| dc.contributor.author-college | 生命科學院 | zh_TW |
| dc.contributor.author-dept | 生命科學系 | zh_TW |
| 顯示於系所單位： | 生命科學系 | |
文件中的檔案：
| 檔案 | 大小 | 格式 | |
|---|---|---|---|
| ntu-107-R05b21009-1.pdf 未授權公開取用 | 10.2 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。