Cytochrome P450 1D1: a novel CYP1A-related gene that is not transcriptionally activated by PCB126 or TCDD.

Cytochrome P450 1D1: a novel CYP1A-related gene that is not transcriptionally activated by PCB126 or TCDD.
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DOI:
10.1016/j.abb.2008.12.002
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发表时间:
2009-02
影响因子:
3.9
通讯作者:
Stegeman, J. J.
Stegeman, J. J.
中科院分区:
生物学3区
文献类型:
--
作者:
Goldstone, J. V.;Joensson, M. E.;Behrendt, L.;Woodin, B. R.;Jenny, M. J.;Nelson, D. R.;Stegeman, J. J.

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细胞色素P4501家族中的酶能氧化许多常见的环境毒物。我们在斑马鱼中发现了一种新的细胞色素P450 1,命名为细胞色素P1D 1。在系统发育上,CyP1d1与CyP1a相似,氨基酸同源性为45%,基因结构相似。在成年斑马鱼中,CYP1D1在肝脏中表达最高,在脑中表达相对较高。在受精后9h,细胞色素P4501的转录水平高于发育后期。用有效的芳香烃受体激动剂(3,3‘,4,4’,5-五氯联苯或2,3,7,8-四氯二苯并-对二恶英)处理斑马鱼不能诱导细胞色素P1D1的转录表达。介导其他CYP1s诱导的AHR2的吗啉寡核苷酸敲除并不影响CyP1d1的表达。在酵母中异源表达的斑马鱼具有乙氧基间苯二酚和甲氧基间苯二酚-O-脱烷基酶活性。针对CYP1D1多肽的抗体在斑马鱼肝微粒体中特异性地检测到一条单一的电泳谱可分辨的蛋白质带,这与CyP1a不同。斑马鱼中的细胞色素P1D1是一种类似于细胞色素P1a的基因,可能具有针对内源化合物的代谢功能。
Enzymes in the cytochrome P450 1 family oxidize many common environmental toxicants. We identified a new CYP1, termed CYP1D1, in zebrafish. Phylogenetically, CYP1D1 is paralogous to CYP1A and the two share 45% amino acid identity and similar gene structure. In adult zebrafish, CYP1D1 is most highly expressed in liver and is relatively highly expressed in brain. CYP1D1 transcript levels were higher at 9 hours post-fertilization than at later developmental times. Treatment of zebrafish with potent aryl hydrocarbon receptor (AHR) agonists (3,3′,4,4′,5-pentachlorobiphenyl or 2,3,7,8-tetrachlorodibenzo-p-dioxin) did not induce CYP1D1 transcript expression. Morpholino oligonucleotide knockdown of AHR2, which mediates induction of other CYP1s, did not affect CYP1D1 expression. Zebrafish CYP1D1 heterologously expressed in yeast exhibited ethoxyresorufin- and methoxyresorufin-O-dealkylase activities. Antibodies against a CYP1D1 peptide specifically detected a single electrophoretically-resolved protein band in zebrafish liver microsomes, distinct from CYP1A. CYP1D1 in zebrafish is a CYP1A-like gene that could have metabolic functions targeting endogenous compounds.
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