Newly Identified Tree Shrew Cytochrome P450 2A13 is Expressed in Liver and Lung and Encodes a Functional Drug-Metabolizing Enzyme Similar to Dog Cytochrome P450 2A13 and Pig Cytochrome P450 2A19

被引：7

作者：

Ushirozako, Genki ^{[1
]}

Noda, Yutaro ^{[2
]}

Murayama, Norie ^{[2
]}

Kawaguchi, Hiroaki ^{[3
]}

Tsukiyama-Kohara, Kyoko ^{[4
,5
]}

Yamazaki, Hiroshi ^{[2
,7
]}

Uno, Yasuhiro ^{[1
,6
]}

机构：

[1] Kagoshima Univ, Joint Fac Vet Med, Kagoshima, Japan

[2] Showa Pharmaceut Univ, Tokyo, Japan

[3] Kitasato Univ, Sch Vet Med, Aomori, Japan

[4] Kagoshima Univ, Joint Fac Vet Med, Transboundary Anim Dis Ctr, Kagoshima, Japan

[5] Kagoshima Univ, Joint Fac Vet Med, Lab Anim Hyg, Kagoshima, Japan

[6] Kagoshima Univ, Joint Fac Vet Med, 1-21-24 Korimoto, Kagoshima, Kagoshima 8900065, Japan

[7] Showa Pharmaceut Univ, Lab Drug Metab & Pharmacokinet, 3-3165 Higashi Tamagawa Gakuen, Tokyo 1948543, Japan

来源：

DRUG METABOLISM AND DISPOSITION | 2023年 / 51卷 / 05期

基金：

日本学术振兴会;

关键词：

AMINO-ACID; ANIMAL-MODEL; CYTOCHROME-P450; POLYMORPHISMS; OXIDATION; RESIDUES; CYP2A13; HUMANS; GENES; MOUSE;

D O I：

10.1124/dmd.122.001152

中图分类号：

R9 [药学];

学科分类号：

1007 ;

摘要：

The tree shrew, a non-rodent primate-like species, is used in various fields of biomedical research, including hepatitis virus infection, myo-pia, depression, and toxicology. Recent genome analysis found that the numbers of cytochrome P450 (P450 or CYP) genes are similar in tree shrews and humans and their sequence identities are high. Al-though the P450s are a family of important drug-metabolizing en-zymes, they have not yet been fully investigated in tree shrews. In the current study, tree shrew CYP2A13 cDNA was isolated from liver, and its characteristics were compared with those of pig, dog, and human CYP2As. Tree shrew CYP2A13 amino acid sequences were highly identical (87-92%) to the human CYP2As and contained sequence mo-tifs characteristic of P450s. Phylogenetic analysis revealed that tree shrew CYP2A13 was more closely related to human CYP2As than to rat CYP2As, similar to dog and pig CYP2As. Among the tissue types analyzed, tree shrew CYP2A13 mRNA was preferentially expressed in liver and lung, similar to dog CYP2A13 mRNA, whereas dog CYP2A25 and pig CYP2A19 mRNAs were predominantly expressed in liver. Tree shrew liver microsomes and tree shrew CYP2A13 proteins heterolo-gously expressed in Escherichia coli catalyzed coumarin 7 -hydroxyl-ation and phenacetin O-deethylation, just as human, dog, and pig CYP2A proteins and liver microsomes do. These results demonstrate that tree shrew CYP2A13 is expressed in liver and lung and encodes a functional drug-metabolizing enzyme.

引用

页码：610 / 617

页数：8

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