Xenobiotic-Metabolism and Steroidogenic Enzyme Cytochrome P450 and Their Regulation---Bioinformatic and Functional Genomic Approach (I)

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基本資料

Project title

Code/計畫編號

NSC96-2627-B019-001

Translated Name/計畫中文名

環境異質代謝與固醇合成酵素細胞色素P450 及其調控---生物資訊與功能基因體學探討---總計畫：生物資訊與功能基因體學探討(I)

Project Coordinator/計畫主持人

Chin-Hwa Hu

Funding Organization/主管機關

National Science and Technology Council

Co-Investigator(s)/共同執行人

白敦文
張大慈
李立安
陳逸然
鄒文雄

Department/Unit

Department of Bioscience and Biotechnology

Website

https://www.grb.gov.tw/search/planDetail?id=1467799

Year

2007

Start date/計畫起

01-08-2007

Expected Completion/計畫迄

01-07-2008

Co-Investigator(s)

Wen-Shyong Tzou

Bugetid/研究經費

1659千元

ResearchField/研究領域

生物技術(理)

" Cytochrome P450 是一群含有原血紅素（heme）輔基的單氧氧化.，參與生物體內各項的氧化代謝反應，普遍存在於各種生物個體中。一般而言，這些酵素大致可分為體內內生性物質氧化代謝以及環境異質類與藥物代謝兩種，後者包括有CYP1~3 類，其基因的表現分別接受細胞核接受器（nuclear receptor）如AHR、CAR 與PXR 的調控。在另一方面，參與固醇類荷爾蒙的合成酵素細胞色素P450，包括CYP11 (P450scc)、CYP17、CYP19 與CYP21，其中CYP11 是固醇合成反應中的速率決定因子。細胞核接受器SF-1 控制各固醇類荷爾蒙的合成酵素細胞色素P450 基因的表現。在本計畫中，我們將結合生物資訊分析以及各種功能性基因體學的方法來探討環境異質代謝與固醇合成酵素細胞色素P450 的結構、調控與生物功能。在本計畫中，我們將著重在下列各項的研究： 1. 環境異質代謝與固醇合成酵素細胞色素P450 基因在斑馬魚胚胎發育時期的調控與生物功能。 2. 參與調控P450 基因的細胞核接受器AHR、PXR 與其細胞傳遞系統在胚胎發育過程中的功能。 3. 針對P450 及其相關分子網路進行基因表現分析，建立P450 基因調控網路。 4. 鑑定各P450 基因保守性調控子與microRNA 辨識序列。 5. 探討人類CYP11B1 與CYP11B2 基因上之L1 轉位子以及其他高保守DNA 序列之功能。 6. 脊椎動物固醇合成酵素細胞色素P450 基因演化分析。 7. P450 蛋白序列之組合式特徵擷取與結構表面比對。 " " The Cytochrome P450 super-family is a fundamental requirement for the viability of most life, with Cytochrome P450 proteins having been identified in organisms ranging from bacteria to man. These enzymes may be subdivided into those that metabolise purely endogenous chemicals, and those that are involved in xenobiotic metabolism. Of the latter group it consists of highly conserved CYP1-3 sub-families and they are regulated by nuclear receptors aryl hydrocarbon recpetor (AHR), constitutive androstane receptor (CAR) and pregnane-X receptor (PXR), respectively. Of the steroidogenic enzymes, it consists of CYP11 (P450SCC), CYP17, CYP19 (aromatase) and CYP21 sub-families, in which the CYP11 controls the first and rate-limiting step of steroid biosynthesis. Nuclear receptor SF-1 plays a major role in determining the cell-specific expression of P450 steroidogenic enzymes. In this proposal, we would like to investigate the structure, regulation and function of zebrafish xenobiotic metabolic and steroidogenic enzyme P450s through bioinformatics and various functional genomic approaches. Here we would like to focus on the following subjects: 1. Genetic regulation and biological function of xenobiotics metabolism and steroidogenic enzyme cytochrome P450 genes during zebrafish developing stages. 2. Delineate functions and interaction of AHR and PXR signaling pathways in zebrafish development. 3. Profile the gene expression and conduct a computational genomic investigation to delineate the gene-regulatory network of cytochrome P450 subfamily 1and 3. 4. Identify the consensus cis-elements upon which transcription factors and microRNAs exert. 5. Delineate the impact of L1 transposition and the role of conserved DNA elements in CYP11B1 and CYP11B2 gene regulation. 6. Develop versatile and integrated bioinformatics tools for the collaborating research in biological areas. "

Keyword(s)

Cytochrome P450
CYP1, CYP3, CYP11
regulatory network
Aryl hydrocarbon receptor
pregnane-X receptor

DSpace CRIS

Xenobiotic-Metabolism and Steroidogenic Enzyme Cytochrome P450 and Their Regulation---Bioinformatic and Functional Genomic Approach (I)

基本資料

Description