Functions of Pxr and Bhlh-Pas Genes in Fish Gastrointestinal Tract Developmnet (II)

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基本資料

Project title

Code/計畫編號

NSC95-2313-B019-010

Translated Name/計畫中文名

PXR與bHLH-PAS基因對於魚類消化器官發育的功能(II)

Project Coordinator/計畫主持人

Chin-Hwa Hu

Funding Organization/主管機關

National Science and Technology Council

Department/Unit

Department of Bioscience and Biotechnology

Website

https://www.grb.gov.tw/search/planDetail?id=1286788

Year

2006

Start date/計畫起

01-08-2006

Expected Completion/計畫迄

01-07-2007

Bugetid/研究經費

1408千元

ResearchField/研究領域

生物科學

Cytochrome P450 1B1 (CYP1B1)為一含有heme的單氧氧化酶，可對多種多環芳香族碳氫化合物、芳香胺、視黃酸以及固醇類荷爾蒙進行代謝。在本研究中我們選殖出斑馬魚的CYP1B1基因，並且發現在胚胎發育時期該基因受到兩種不同機制調控。首先在孵化前，斑馬魚CYP1B1基因會在視網膜、中後腦中隔以及端腦區進行AHR非依賴性持續表現，但是活化的AHR會增強視網膜中此類型的表現活性。孵化後此類型的表現逐漸消退，同時活化的AHR亦無法挽回，但是受TCDD活化的AHR卻可在仔魚的鰓弧與心臟區域誘發新的CYP1B1的表現。將AHR2基因弱化降低蛋白質轉譯作用後會中止TCDD所誘發的CYP1B1的表現。除了上述區域外，我們並未在胚胎發育期間發現CYP1B1在肝腎區域的表現。以上實驗顯示CYP1B1在胚胎內由不同的機制調控組織專一性的表現。此外，我們亦針對CYP1B1在TCDD胚胎毒性的作用上的腳色進行探討。實驗結果顯示將CYP1B1基因弱化並不會阻止TCDD所造成的圍心腔膨大以及顱面頭骨缺失等毒性作用，顯示CYP1B1並未參予TCDD的胚胎毒性作用。Cytochrome P450 1B1 (CYP1B1) is a heme-containing monooxygenase that metabolizes various polycyclic aromatic hydrocarbons (PAHs) and arylamines, as well as retinoic acid and steroid hormones. Here we cloned an ortholog of CYP1B1 from zebrafish and presented that transcription of zebrafish CYP1B1 is modulated by two types of mechanisms during different stages of development. First in late pharyngula stage before hatching, CYP1B1 is constitutively transcribed in retina, midbrain-hindbrain boundary (MHB) and telencephalon regions through an AHR2-independent pathway. The ligand-activated AHR2 has a synergistic function to enhance the basal level of transcription in ocular cells. After hatching, the constitutive-type CYP1B1 transcription is attenuated and it could not be elicited by TCDD exposure. In contrast, TCDD exposure induced de novo CYP1B1 transcription in larval branchial arches and heart tissues via an AHR2-dependent pathway. Blocking AHR2 translation eliminated the TCDD-induced CYP1B1 transcription. However, we did not detect any types of CYP1B1 transcription in liver and kidney tissues through the developmental stages. It suggests that the constitutive and TCDD-inducible types of CYP1B1 transcriptions are modulated by distinct pathways and exhibit different tissue specificity. Finally, we investigate the role of CYP1B1 in TCDD-mediated embryonic toxicity. It appears that CYP1B1 knockdown did not prevent TCDD-induced pericardial edema and cranial defects, suggesting that CYP1B1 does not involve in the developmental toxicity of dioxin.

Keyword(s)

斑馬魚
CYP1B1
胚胎
AHR2
基因調控
戴奧辛
zebrafish
CYP1B1
embryo
AHR2
gene regulation
TCDD

DSpace CRIS

Functions of Pxr and Bhlh-Pas Genes in Fish Gastrointestinal Tract Developmnet (II)

基本資料

Description