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

被引：67

作者：

Goldstone, J. V. ^{[1
]}

Joensson, M. E. ^{[1
]}

Behrendt, L. ^{[1
]}

Woodin, B. R. ^{[1
]}

Jenny, M. J. ^{[1
]}

Nelson, D. R. ^{[2
]}

Stegeman, J. J. ^{[1
]}

机构：

[1] Woods Hole Oceanog Inst, Dept Biol, Woods Hole, MA 02543 USA

[2] Univ Tennessee, Dept Mol Sci, Memphis, TN USA

来源：

ARCHIVES OF BIOCHEMISTRY AND BIOPHYSICS | 2009年 / 482卷 / 1-2期

基金：

瑞典研究理事会;

关键词：

Development; CYP1D1; AHR; PCB126; TCDD; Zebrafish; Embryo; Vertebrate toxicology; Oxidative biotransformation; ARYL-HYDROCARBON RECEPTOR; MAXIMUM-LIKELIHOOD; HETEROLOGOUS EXPRESSION; DEVELOPMENTAL TOXICITY; PHYLOGENETIC ANALYSIS; ZEBRAFISH EMBRYOS; SUBSTRATE-BINDING; MIXED MODELS; P450; 1A1; 2,3,7,8-TETRACHLORODIBENZO-P-DIOXIN;

D O I：

10.1016/j.abb.2008.12.002

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

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 gone 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 h post-fertilization than it 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-0-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. (c) 2008 Elsevier Inc. All rights reserved.

引用

页码：7 / 16

页数：10

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