新鉴定出的树鼩细胞色素P450 2B6（CYP2B6）和猪CYP2B6b是具有功能的药物代谢酶。
Newly identified tree shrew cytochrome P450 2B6 (CYP2B6) and pig CYP2B6b are functional drug-metabolising enzymes.
作者信息
Uno Yasuhiro, Ushirozako Genki, Uehara Shotaro, Murayama Norie, Fujiki Yuki, Kawaguchi Hiroaki, Tsukiyama-Kohara Kyoko, Yamazaki Hiroshi
机构信息
Department of Basic Veterinary Science, Joint Faculty of Veterinary Medicine, Kagoshima University, Kagoshima, Japan.
Laboratory of Drug Metabolism and Pharmacokinetics, Showa Pharmaceutical University, Machida, Japan.
出版信息
Xenobiotica. 2022 Jul;52(7):687-696. doi: 10.1080/00498254.2022.2141153. Epub 2022 Nov 3.
Tree shrews have high phylogenetic affinity to humans and are used in various fields of biomedical research, especially hepatitis virus infection; however, cytochromes P450 (P450s or CYPs) have not been investigated in this species.In this study, tree shrew CYP2B6 and pig CYP2B6b were newly identified and had amino acid sequences highly identical (80% and 78%, respectively) to human CYP2B6, containing sequence motifs characteristic of P450s.Phylogenetic analysis revealed that novel tree shrew CYP2B6 was more closely related to known human CYP2B6 than dog, pig, or rat CYP2Bs are.Among the tissue types analysed, tree shrew CYP2B6 mRNA was preferentially expressed in liver and lung, whereas pig CYP2B6b mRNA was preferentially expressed in jejunum and lung.Tree shrew CYP2B6 and pig CYP2B6b proteins heterologously expressed in metabolised human CYP2B6 substrates efavirenz, ethoxycoumarin, propofol, and testosterone, suggesting that these novel CYP2Bs are functional drug-metabolizing enzymes in liver and/or lung.
树鼩与人类具有高度的系统发育亲缘关系，被用于生物医学研究的各个领域，尤其是肝炎病毒感染研究；然而，该物种的细胞色素P450（P450或CYP）尚未得到研究。在本研究中，新鉴定出树鼩CYP2B6和猪CYP2B6b，它们与人类CYP2B6的氨基酸序列高度相同（分别为80%和78%），含有P450的特征序列基序。系统发育分析表明，新发现的树鼩CYP2B6与已知的人类CYP2B6的亲缘关系比狗、猪或大鼠的CYP2B更密切。在所分析的组织类型中，树鼩CYP2B6 mRNA在肝脏和肺中优先表达，而猪CYP2B6b mRNA在空肠和肺中优先表达。在代谢人CYP2B6底物依法韦仑、乙氧香豆素、丙泊酚和睾酮时，树鼩CYP2B6和猪CYP2B6b蛋白异源表达，这表明这些新的CYP2B是肝脏和/或肺中的功能性药物代谢酶。
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