Uno Yasuhiro, Hosaka Shinya, Yamazaki Hiroshi
Pharmacokinetics and Bioanalysis Center, Shin Nippon Biomedical Laboratories, Ltd., Kainan, Wakayama 642-0017, Japan.
J Vet Med Sci. 2014 Dec;76(12):1647-50. doi: 10.1292/jvms.14-0313. Epub 2014 Sep 3.
Cytochromes P450 (P450) are important for not only drug metabolism and toxicity, but also biosynthesis and metabolism of cholesterol and bile acids, and steroid synthesis. In cynomolgus macaques, widely used in biomedical research, we have characterized P450 cDNAs, which were isolated as expressed sequence tags of cynomolgus macaque liver. In this study, cynomolgus CYP7A1, CYP17A1, CYP20A1, CYP27A1 and CYP51A1 cDNAs were characterized by sequence analysis, phylogenetic analysis and tissue expression pattern. By sequence analysis, these five cynomolgus P450s had high sequence identities (94-99%) to the human orthologs in amino acids. By phylogenetic analysis, each cynomolgus P450 was more closely related to the human ortholog as compared with the dog or rat ortholog. By quantitative polymerase chain reaction, among the 10 tissue types, CYP7A1 and CYP17A1 mRNAs were preferentially expressed in liver and adrenal gland, respectively. Cynomolgus CYP27A1 and CYP51A1 mRNAs were most abundantly expressed in liver and testis, respectively. Cynomolgus CYP20A1 mRNA was expressed in all the tissues, including brain and liver. Tissue expression patterns of each cynomolgus P450 were generally similar to that of the human ortholog. These results suggest the molecular similarities of CYP7A1, CYP17A1, CYP20A1, CYP27A1 and CYP51A1 between cynomolgus macaques and humans.
细胞色素P450（P450）不仅对药物代谢和毒性很重要，而且对胆固醇和胆汁酸的生物合成与代谢以及类固醇合成也很重要。在生物医学研究中广泛使用的食蟹猴中，我们对P450 cDNA进行了表征，这些cDNA是作为食蟹猴肝脏的表达序列标签分离出来的。在本研究中，通过序列分析、系统发育分析和组织表达模式对食蟹猴CYP7A1、CYP17A1、CYP20A1、CYP27A1和CYP51A1 cDNA进行了表征。通过序列分析，这五种食蟹猴P450在氨基酸水平上与人直系同源物具有高度的序列同一性（94-99%）。通过系统发育分析，与狗或大鼠的直系同源物相比，每种食蟹猴P450与人直系同源物的关系更为密切。通过定量聚合酶链反应，在10种组织类型中，CYP7A1和CYP17A1 mRNA分别在肝脏和肾上腺中优先表达。食蟹猴CYP27A1和CYP51A1 mRNA分别在肝脏和睾丸中表达最为丰富。食蟹猴CYP20A1 mRNA在包括脑和肝脏在内的所有组织中均有表达。每种食蟹猴P450的组织表达模式通常与人类直系同源物相似。这些结果表明食蟹猴和人类之间CYP7A1、CYP17A1、CYP20A1、CYP27A1和CYP51A1在分子上具有相似性。
