Identification and developmental expression of the full complement of Cytochrome P450 genes in Zebrafish.
Identification and developmental expression of the full complement of Cytochrome P450 genes in Zebrafish.
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DOI：
10.1186/1471-2164-11-643
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发表时间：
2010-11-18
期刊：
影响因子：
4.4
通讯作者：
Stegeman JJ
中科院分区：
文献类型：
--
作者：
Goldstone JV;McArthur AG;Kubota A;Zanette J;Parente T;Jönsson ME;Nelson DR;Stegeman JJ
斑马鱼在药物发现和机制毒理学中的应用越来越多，这需要了解细胞色素P450（CYP 450）基因的调控和功能。氧化酶催化氧化转化，导致许多内源性和外源性化学物质的活化或失活，对正常生理和疾病过程产生影响。许多CYP可能在发育规范中发挥作用，许多导致发育异常的化学物质是CYP的底物。在这里，我们确定和注释的全套斑马鱼中的flip-flop基因，比较这些人的flip-flop基因互补，并确定在正常发育过程中的flip-flop基因的表达。斑马鱼共有94个基因，分布在哺乳动物中发现的18个基因家族中。在CYP家族5至51中有32个基因，其中大多数是参与内源性功能（包括调节分子的合成或失活）的人CYP的直接直系同源物。高度的序列相似性表明这些CYP的酶活性保守，这在一些类固醇生成酶（例如CYP 19，芳香酶; CYP 11 A，P450 SCC; CYP 17，类固醇17 α-羟化酶）和CYP 26视黄酸羟化酶的报告中得到证实。复杂性在基因家族1、2和3中要大得多，其中包括在药物和污染物代谢以及内源性底物代谢中突出的CYP。斑马鱼与人类的某些CYP 1和CYP 3基因存在亲缘关系。相比之下，斑马鱼有47个CYP 2基因，而人类有16个，只有两个（CYP 2 R1和CYP 2U 1）被认为是基于序列的正向同源。共享的同线性分析确定了与哺乳动物CYP 2进化相关的CYP 2基因簇，以及独特的簇。通过微阵列和定量PCR的转录谱分析显示，大多数斑马鱼的hepatocytes基因在胚胎中表达，在发育过程中不同基因组的表达呈波浪状。一些转录本也发生在卵母细胞中。研究结果为斑马鱼作为毒理学、药理学和化学疾病研究的模型提供了基础。
Increasing use of zebrafish in drug discovery and mechanistic toxicology demands knowledge of cytochrome P450 (CYP) gene regulation and function. CYP enzymes catalyze oxidative transformation leading to activation or inactivation of many endogenous and exogenous chemicals, with consequences for normal physiology and disease processes. Many CYPs potentially have roles in developmental specification, and many chemicals that cause developmental abnormalities are substrates for CYPs. Here we identify and annotate the full suite of CYP genes in zebrafish, compare these to the human CYP gene complement, and determine the expression of CYP genes during normal development. Zebrafish have a total of 94 CYP genes, distributed among 18 gene families found also in mammals. There are 32 genes in CYP families 5 to 51, most of which are direct orthologs of human CYPs that are involved in endogenous functions including synthesis or inactivation of regulatory molecules. The high degree of sequence similarity suggests conservation of enzyme activities for these CYPs, confirmed in reports for some steroidogenic enzymes (e.g. CYP19, aromatase; CYP11A, P450scc; CYP17, steroid 17a-hydroxylase), and the CYP26 retinoic acid hydroxylases. Complexity is much greater in gene families 1, 2, and 3, which include CYPs prominent in metabolism of drugs and pollutants, as well as of endogenous substrates. There are orthologous relationships for some CYP1 s and some CYP3 s between zebrafish and human. In contrast, zebrafish have 47 CYP2 genes, compared to 16 in human, with only two (CYP2R1 and CYP2U1) recognized as orthologous based on sequence. Analysis of shared synteny identified CYP2 gene clusters evolutionarily related to mammalian CYP2 s, as well as unique clusters. Transcript profiling by microarray and quantitative PCR revealed that the majority of zebrafish CYP genes are expressed in embryos, with waves of expression of different sets of genes over the course of development. Transcripts of some CYP occur also in oocytes. The results provide a foundation for the use of zebrafish as a model in toxicological, pharmacological and chemical disease research.
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影响因子：
--
作者：
Gu, Xingxing;Xu, Fang;Zhao, Qingshun
通讯作者：
Zhao, Qingshun
影响因子：
3.9
作者：
Choudhary, D;Jansson, I;Schenkman, JB
通讯作者：
Schenkman, JB
DOI：
10.1016/s0960-0760(01)00147-9
发表时间：
2001-12-01
影响因子：
4.1
作者：
Callard, GV;Tchoudakova, AV;Wood, E
通讯作者：
Wood, E
影响因子：
3.9
作者：
Goldstone, J. V.;Joensson, M. E.;Behrendt, L.;Woodin, B. R.;Jenny, M. J.;Nelson, D. R.;Stegeman, J. J.
通讯作者：
Stegeman, J. J.
影响因子：
3.9
作者：
Choudhary, D;Jansson, I;Stoilov, I
通讯作者：
Stoilov, I