Laboratory of Drug Metabolism and Pharmacokinetics, Showa Pharmaceutical University, Machida, Japan.
Joint Faculty of Veterinary Medicine, Kagoshima University, Kagoshima-city, Japan.
Drug Metab Pharmacokinet. 2021 Aug;39:100398. doi: 10.1016/j.dmpk.2021.100398. Epub 2021 Apr 17.
Paraoxonase (PON) plays roles in the metabolism of organophosphate xenobiotics and drugs. Despite the importance of marmosets for research into drug metabolism and pharmacokinetics, marmoset paraoxonase has not yet been fully characterized. Consequently, we identified the PON1 gene in the marmoset genome by sequence homology analysis. Marmoset PON1 cDNA containing an open reading frame (1065 bp) was successfully cloned from marmoset liver by reverse transcription-polymerase chain reaction. The deduced amino acid sequence (355 amino acids) has approximately 93% identity with the human ortholog and contains important amino acid residues for substrate binding and calcium ion coordination. According to a phylogenetic tree of PON1 amino acid sequences constructed using data from seven animal species, marmoset PON1 is closer to human PON1 than it is to the PON1 orthologs of experimental animals such as pigs, rabbits, rats, and mice. Marmoset PON1 mRNA was predominantly expressed in liver among the five tissues examined. Marmoset PON1 protein secreted into plasma was detected by immunoblotting. The paraoxon-hydrolyzing activity in plasma was higher in marmosets than in humans. Based on these data, we concluded that marmoset and human PON1 have similar characteristics with regard to genomic structure, amino acid sequences, and tissue distribution.
对氧磷酶（PON）在有机磷异生物和药物的新陈代谢中发挥作用。尽管绒猴在药物新陈代谢和药代动力学的研究中具有重要意义，但绒猴的对氧磷酶尚未得到充分的描述。因此，我们通过序列同源性分析在绒猴基因组中鉴定了 PON1 基因。我们通过反转录-聚合酶链反应成功地从绒猴肝脏中克隆了含有开放阅读框（1065bp）的 PON1 cDNA。推导的氨基酸序列（355 个氨基酸）与人类同源物具有约 93%的同一性，并且包含重要的氨基酸残基，用于底物结合和钙离子配位。根据来自七个动物物种的 PON1 氨基酸序列构建的系统进化树，绒猴 PON1 与人类 PON1 比与实验动物（如猪、兔、大鼠和小鼠）的 PON1 同源物更接近。在检查的五个组织中，PON1 mRNA 在肝脏中主要表达。通过免疫印迹检测到分泌到血浆中的 PON1 蛋白。与人类相比，血浆中的对氧磷水解活性在绒猴中更高。根据这些数据，我们得出结论，绒猴和人类 PON1 在基因组结构、氨基酸序列和组织分布方面具有相似的特征。
