碩士 / 國立臺灣海洋大學 / 生物科技研究所 / 93 / Abstract
Cytochrome P450 (CYPs) are a superfamily of heme-containing monooxygenases that metabolize foreign compounds including xenobiotics and drugs, as well as endogenuous compounds such as fatty acid and steroids. Family 1, 2, 3, and 4 are generally designated as drug detoxification enzymes due to their considerable abilities to metabolize xenobiotic compounds. In human, CYP3A isoforms are involved in the metabolism of more than 60% drugs. Up to date, two members of family 3 were identified in zebrafish, CYP3A65 and CYP3C1. Like mammalian CYP3A genes, CYP3A65 mRNA was initially transcribed in the liver and intestine tissues during hatching stages and CYP3A65 transcription in the intestine was enhanced by treatment with the steroid dexamethasone (DEX) or rifampicin (RIF). In addition, the CYP3A65 transcription was also enhanced by treatment with tetrachloro-dibenzo-p-dioxin (TCDD) during early larval stages. Repression of AHR2 translation by antisense morpholino oligonucleotides abrogated both of constitutive and TCDD-stimulated CYP3A65 transcription in larval intestine tissue. This finding revealed that the regulation of CYP3A65 is more complex than mammalian CYP3A genes (Tseng et al., 2005). In this study, I have cloned CYP3C1 gene and its encoded amino acid sequence shares significant similarity with CYP3A65, that is 48％ identity and 61％ similarity. In zebrafish embryo, CYP3C1 mRNA was initially transcribed in the intestine at hatching stage. In early stage, the CYP3C1 mRNA was also constitutively expressed in the head region. Differing from CYP3A65, CYP3C1 transcription was not greatly enhanced by dexamethasone, rifampicin, or TCDD treatment during embryonic stages. In mammals, the CYP3A genes are modulated by the PXR-RXR signaling pathway. Here we showed that the CYP3A65, but not CYP3C1, transcription in the intestine was greatly reduced by repression of PXR or AHR2 translation via applying antisense morpholino oligonucleotides. Neverless, the PXR transcription was not changed by AHR2 repression. It suggests that that the AHR2 signaling pathway plays an essential role in regulation of CYP3A65 transcription which is not controlled by modulation of PXR gene expression.
| Identifer | oai:union.ndltd.org:TW/093NTOU5111018 |
| Date | January 2005 |
| Creators | Hsiao-Ting Su, 蘇小婷 |
| 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 | 109 |
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