Jönsson Maria E, Orrego Rodrigo, Woodin Bruce R, Goldstone Jared V, Stegeman John J
Biology Department, Woods Hole Oceanographic Institution, Woods Hole, MA 02543, USA.
Toxicol Appl Pharmacol. 2007 May 15;221(1):29-41. doi: 10.1016/j.taap.2007.02.017. Epub 2007 Mar 12.
The cytochrome P4501C (CYP1C) gene subfamily was recently discovered in fish, and zebrafish (Danio rerio) CYP1C1 transcript has been cloned. Here we cloned the paralogous CYP1C2, showing that the amino acid sequence is 78% identical to CYP1C1, and examined gene structure and expression of CYP1A, CYP1B1, CYP1C1, and CYP1C2. Xenobiotic response elements were observed upstream of the coding regions in all four genes. Zebrafish adults and embryos were exposed (24 h) to 100 nM 3,3',4,4',5-polychlorinated biphenyl (PCB126) or 20 ppm acetone and subsequently held in clean water for 24 h (adults) or 48 h (embryos). All adult organs examined (eye, gill, heart, liver, kidney, brain, gut, and gonads) and embryos showed basal expression of the four genes. CYP1A was most strongly expressed in liver, whereas CYP1B1, CYP1C1, and CYP1C2 were most strongly expressed in heart and eye. CYP1B1 and the CYP1C genes showed an expression pattern similar to one another and to mammalian CYP1B1. In embryos CYP1C1 and CYP1C2 tended to have a higher basal expression than CYP1A and CYP1B1. PCB126 induced CYP1A in all organs, and CYP1B1 and CYP1C1 in all organs except gonads, or gonads and brain, respectively. CYP1C2 induction was significant only in the liver. However, in embryos all four genes were induced strongly by PCB126. The results are consistent with CYP1C1 and CYP1C2, as well as CYP1A and CYP1B1, being regulated by the aryl hydrocarbon receptor. While CYP1A may have a protective role against AHR agonists in liver and gut, CYP1B1, CYP1C1, and CYP1C2 may also play endogenous roles in eye and heart and possibly other organs, as well as during development.
细胞色素P4501C（CYP1C）基因亚家族最近在鱼类中被发现，斑马鱼（Danio rerio）的CYP1C1转录本已被克隆。在此，我们克隆了其旁系同源基因CYP1C2，结果显示其氨基酸序列与CYP1C1有78%的同一性，并对CYP1A、CYP1B1、CYP1C1和CYP1C2的基因结构及表达进行了研究。在所有这四个基因的编码区上游均观察到了外源性反应元件。将成年斑马鱼和胚胎暴露于100 nM的3,3',4,4',5-多氯联苯（PCB126）或20 ppm丙酮中24小时，随后在清洁水中饲养24小时（成年鱼）或48小时（胚胎）。所检测的所有成年器官（眼睛、鳃、心脏、肝脏、肾脏、大脑、肠道和性腺）以及胚胎均显示出这四个基因的基础表达。CYP1A在肝脏中表达最强，而CYP1B1、CYP1C1和CYP1C2在心脏和眼睛中表达最强。CYP1B1和CYP1C基因显示出彼此相似且与哺乳动物CYP1B1相似的表达模式。在胚胎中，CYP1C1和CYP1C2的基础表达往往高于CYP1A和CYP1B1。PCB126在所有器官中诱导CYP1A表达，在除性腺外的所有器官中诱导CYP1B1表达，在性腺和大脑中分别诱导CYP1C1表达。CYP1C2的诱导仅在肝脏中显著。然而，在胚胎中所有这四个基因均被PCB126强烈诱导。这些结果与CYP1C1和CYP1C2以及CYP1A和CYP1B1受芳烃受体调控一致。虽然CYP1A可能在肝脏和肠道中对AHR激动剂具有保护作用，但CYP1B1、CYP1C1和CYP1C2可能在眼睛、心脏以及可能的其他器官中以及在发育过程中也发挥内源性作用。
