博士 / 國立臺灣海洋大學 / 生物科技研究所 / 92 / Abstract
During embryogenesis, all of the processes of cell differentiation,organogenesis and response to environmental stimulation are controlled byserious gene regulation systems. The bHLH-PAS （Per-AhR/Arnt-Sim）protein family plays important roles in vertebrate development and xenobiotic metabolism. In the bHLH-PAS mediated pathway, Arnt proteinplays as a central role, which can dimerizes with other bHLH-PAS（such as AHR, HIF, and SIM）to regulate a variety genes. The heterodimer complex of AHR::ARNT is an ubiquitous transcription factor which mediates the expression of xenobiotic-response genes, such as cytochrome p450 1a1 (cyp1a1) and cyp1a2. Previously, we obtained cDNA of two truncated ARNT factor, arnt2a and arnt2x, both of their encoded proteins contain the highly conserved bHLH and PAS A/B domains, but they all lack a conventional transactivation domain at carboxyl end. In cultured ZLE cells, transiently expressed ARNT2A and ARNT2X inhibited 2,3,7,8-TCDD-activated cyp1a1 transcription with different
efficiencies. Four arnt2 cDNA were cloned in zebrafish, named arnt2a, arnt2b, arnt2c, and arnt2x. arnt2a/b/c mRNAs were exited in the mature oocytes as materal mRNA and expressed during embryogenesis. To investigate the function of ARNT2A/B/C, I have employed gene-specific antisense morpholino oligonucleotide to block ARNT2A/B/C protein
translation. Injecting of arnt2a/b/c antisense morpholino into fertilized embryos at 1 cell stage led to malformation of craniofacial skeleton. Craniofacial skeleton is formed by cells that are derived from ectoderm, endoderm, mesoderm. Injection of arnt2a/b/c antisense morpholino into
embryo led to reduce the amount of cranial neural crest cell, but didn’t disrupt the muscle and pharyngeal pouches formation.
The aryl hydrocarbon receptor （AHR ） is a ligand-dependent
transcription factor that belongs to the basic-helix-loop-helix PAS （bHLH-PAS） family. The AHR can be activated by a diverse synthetic and naturally-occurring chemicals, such as halogenated aromatic hydrocarbons （HAHs） and the non- halogenated polycyclic aromatic hydrocarbons （PAHs）. The liganded AHR modulates the genetic activity of a variety of xenobiotic-responsive gene, including cyp1a1. Here, I
showed evidence that 0.2 mM PTU induced a basal level of cyp1a1 transcription in blood vessels at 36 hpf. During larval stage, the liver and all pharyngeal arch vessels of PTU-treated embryos exhibited cyp1a1 transcription as well. Coincubating the embryos with PTU and TCDD led to epressing TCDD-induced cyp1a1 transcription. Mechanistic studies
indicated that both of PTU- and TCDD- mediated cyp1a1 transcriptions are modulated by the same AHR-ARNT signaling pathway.
| Identifer | oai:union.ndltd.org:TW/092NTOU5111012 |
| Date | January 2004 |
| Creators | Wen-Der Wang, 王文德 |
| Contributors | Chin-Hwa Hu, 胡清華 |
| Source Sets | National Digital Library of Theses and Dissertations in Taiwan |
| Language | zh-TW |
| Detected Language | English |
| Type | 學位論文 ; thesis |
| Format | 157 |
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