Shaya Lana, Dejong Chris, Wilson Joanna Y
Department of Biology, McMaster University, 1280 Main Street West, Hamilton, ON L8S 4K1, Canada.
Comp Biochem Physiol C Toxicol Pharmacol. 2014 Nov;166:115-25. doi: 10.1016/j.cbpc.2014.06.008. Epub 2014 Jul 27.
Cytochrome P450 (CYP) 3 enzymes are highly expressed in detoxification organs and play an important role in xenobiotic metabolism. In fish, the CYP3 family is diversified and includes several subfamilies (CYP3B, CYP3C, and CYP3D) not found in mammals. The functional role and expression patterns of these novel genes are unknown. In this study, the expression patterns of novel teleost CYP3 genes were determined in medaka(Oryzias latipes; CYP3B4, CYP3B5, CYP3B6) and zebrafish (Danio rerio; CYP3C1, CYP3C2, CYP3C3, CYP3C4), two important model fish species. Expression was quantified with real time PCR in multiple internal organs from adult male and female fish. CYP3C gene expression was determined in zebrafish embryos. Expression in all organs was detected for all genes, except for CYP3B4 in male organs. CYP3C1, CYP3C3, CYP3B4, CYP3B5, and CYP3B6 were more highly expressed in liver and/or intestine from at least one gender, suggesting a role in xenobiotic metabolism. Expression of CYP3C1 and CYP3B5 in olfactory rosette was comparable to liver. CYP3C1, CYP3C4, CYP3B5 and CYP3B6 expression was higher in the female organs; CYP3C2 and CYP3B5 were higher in testis. Estrogen and androgen response elements were found upstream of the start site of many of these genes raising the hypothesis that they are under steroid regulation. CYP3C1-3 were expressed in all developmental stages examined and appear to be maternally deposited. The expression patterns suggest that some of these CYP genes are involved in xenobiotic metabolism.
细胞色素P450(CYP)3酶在解毒器官中高度表达,在异源物质代谢中起重要作用。在鱼类中,CYP3家族具有多样性,包括几个在哺乳动物中未发现的亚家族(CYP3B、CYP3C和CYP3D)。这些新基因的功能作用和表达模式尚不清楚。在本研究中,在两种重要的模式鱼类——青鳉(Oryzias latipes;CYP3B4、CYP3B5、CYP3B6)和斑马鱼(Danio rerio;CYP3C1、CYP3C2、CYP3C3、CYP3C4)中确定了新的硬骨鱼CYP3基因的表达模式。通过实时PCR对成年雄鱼和雌鱼的多个内部器官中的表达进行了定量。在斑马鱼胚胎中测定了CYP3C基因的表达。除雄性器官中的CYP3B4外,所有基因在所有器官中均检测到表达。CYP3C1、CYP3C3、CYP3B4、CYP3B5和CYP3B6在至少一种性别的肝脏和/或肠道中表达更高,表明其在异源物质代谢中起作用。CYP3C1和CYP3B5在嗅叶中的表达与肝脏相当。CYP3C1、CYP3C4、CYP3B5和CYP3B6在雌性器官中的表达更高;CYP3C2和CYP3B5在睾丸中的表达更高。在许多这些基因的起始位点上游发现了雌激素和雄激素反应元件,这提出了它们受类固醇调节的假说。CYP3C1 - 3在所有检测的发育阶段均有表达,并且似乎是母源沉积的。这些表达模式表明其中一些CYP基因参与了异源物质代谢。