| Summary: | 碩士 === 國立臺灣海洋大學 === 生物科技研究所 === 94 === Abstract
Cytochrome P450(CYP) are a superfamily of heme-thiolate containing mono-oxygenases involved in the oxidative metabolism of a diverse range of compounds, including steroid hormone ,fatty acids, and toxicants. Members of CYP1, CYP2, and CYP3 family are responsible for a variety of xenobiotics and drug metabolism. In previously study, it was shown that TCDD could enhance zebrafish CYP1A1, CYP1C1and CYP3A65 transcription during larva stages. It suggests that TCDD modulates various CYP genes in fish. Here I have investigated that the TCDD effects in zebrafish CYP2AD3, CYP2V1 and ahrr genes. According to the results of phylogenetic analysis, CYP2AD3 and CYP2V1 derive from a common ancient gene and they share high similarity in their amino acid sequence. However, here I found that CYP2AD3 and CYP2V1 have different regulation mechanism during embryonic development.
Here I presented that TCDD induced novel CYP2AD3 expression in brain and enhanced endogenous CYP2AD3 gene expression in the liver at 120 hpf stage. Repressing AHR2 translation by using gene-specific antisense morpholino oligonucleotide eliminated the TCDD-mediated CYP2AD3 enhancement. It suggested that TCDD induced CYP2AD3 transcriptional activity through an AHR2-dependent pathway. By contrast, TCDD treatment decreased CYP2V1 expression slightly at 96hpf stage and AHR2-knockdown prevented TCDD-mediated CYP2V1 repression. It suggested that TCDD may repress CYP2V1 transcription via an AHR2-dependent mechanism.
In this presentation, I have also shown that zebrafish ahrr1 and ahrr2 genes had different responses to TCDD exposure. It appears that ahrr2 is more sensitive to TCDD than ahrr1. TCDD induced ahrr1 and ahrr2 expression in the ventral diencephalons region by an AHR2-dependent mechanism. AHR2-loss-of-function repressed the endogenous ahrr2, but not ahrr1, transcription at 96 hpf stage. It suggests that AHR2-related signaling pathway involves in endogenous ahrr2 transcription.
|
|---|
