Goldstone J V, Jönsson M E, Behrendt L, Woodin B R, Jenny M J, Nelson D R, Stegeman J J
Biology Department, Woods Hole Oceanographic Institution, Woods Hole, MA, USA.
Arch Biochem Biophys. 2009 Feb;482(1-2):7-16. doi: 10.1016/j.abb.2008.12.002. Epub 2008 Dec 10.
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 9h 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.
细胞色素P450 1家族中的酶可氧化许多常见的环境毒物。我们在斑马鱼中鉴定出一种新的CYP1，命名为CYP1D1。在系统发育上，CYP1D1与CYP1A是旁系同源基因，二者氨基酸序列一致性为45%，且基因结构相似。在成年斑马鱼中，CYP1D1在肝脏中表达量最高，在脑中也有较高表达。受精后9小时CYP1D1的转录水平高于发育后期。用强效芳烃受体（AHR）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）处理斑马鱼不会诱导CYP1D1转录本表达。介导其他CYP1诱导的AHR2的吗啉代寡核苷酸敲低不影响CYP1D1的表达。在酵母中异源表达的斑马鱼CYP1D1表现出乙氧异吩恶唑酮和甲氧基异吩恶唑酮-O-脱烷基酶活性。针对CYP1D1肽段的抗体在斑马鱼肝脏微粒体中特异性检测到一条电泳分离的单一蛋白带，与CYP1A不同。斑马鱼中的CYP1D1是一个类似CYP1A的基因，可能具有针对内源性化合物的代谢功能。
