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Marmoset pulmonary cytochrome P450 2F1 oxidizes biphenyl and 7-ethoxycoumarin and hepatic human P450 substrates.
Xenobiotica. 2018 Jul; 48(7):656-662.X

Abstract

1. A potentially useful animal model for preclinical studies is the common marmoset (Callithrix jacchus). In this study, using reverse-transcription polymerase chain reaction from marmoset livers, we identified a novel cytochrome P450 (P450) 2F1 cDNA with an open reading frame of 1473 bp. 2. High sequence identities of 92-94% with primate P450 2 F amino acid sequences were indicated by deduced amino acid sequences of P450 2F1 cDNA. Phylogenetic analysis indicates that marmoset P450 2F1 is more congruent with primate P450 2 F forms than those of other species such as rodents. 3. Among five tissue types examined, abundant expression of marmoset P450 2F1 mRNA and P450 2F1 protein in lungs was shown. Cynomolgus monkey P450 2F1 mRNA was abundantly expressed in lungs as well as testes and ovaries in 10 tissue types. 4. Similar to those of humans and cynomolgus monkeys, marmoset P450 2F1 heterologously expressed in Escherichia coli membranes efficiently catalyzed 7-ethoxycoumarin O-deethylation and biphenyl hydroxylation, however unlike human P450 2F1, marmoset P450 2F1 exhibited hydroxylation activity toward coumarin and chlorzoxazone. 5. These findings indicated that P450 2F1 enzyme expressed in marmoset lungs and also catalyzed metabolism of xenobiotics, suggesting the importance of P450 2 F-dependent drug metabolism in marmoset lungs.

Authors+Show Affiliations

a Laboratory of Drug Metabolism and Pharmacokinetics , Showa Pharmaceutical University , Machida , Tokyo , Japan.b Pharmacokinetics and Bioanalysis Center, Shin Nippon Biomedical Laboratories, Ltd , Kainan , Wakayama , Japan.a Laboratory of Drug Metabolism and Pharmacokinetics , Showa Pharmaceutical University , Machida , Tokyo , Japan.c Department of Applied Developmental Biology , Central Institute for Experimental Animals , Kawasaki , Japan , and.c Department of Applied Developmental Biology , Central Institute for Experimental Animals , Kawasaki , Japan , and. d Keio Advanced Research Center, Keio University , Minato-ku, Tokyo , Japan.a Laboratory of Drug Metabolism and Pharmacokinetics , Showa Pharmaceutical University , Machida , Tokyo , Japan.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

28689458

Citation

Uehara, Shotaro, et al. "Marmoset Pulmonary Cytochrome P450 2F1 Oxidizes Biphenyl and 7-ethoxycoumarin and Hepatic Human P450 Substrates." Xenobiotica; the Fate of Foreign Compounds in Biological Systems, vol. 48, no. 7, 2018, pp. 656-662.
Uehara S, Uno Y, Oshio T, et al. Marmoset pulmonary cytochrome P450 2F1 oxidizes biphenyl and 7-ethoxycoumarin and hepatic human P450 substrates. Xenobiotica. 2018;48(7):656-662.
Uehara, S., Uno, Y., Oshio, T., Inoue, T., Sasaki, E., & Yamazaki, H. (2018). Marmoset pulmonary cytochrome P450 2F1 oxidizes biphenyl and 7-ethoxycoumarin and hepatic human P450 substrates. Xenobiotica; the Fate of Foreign Compounds in Biological Systems, 48(7), 656-662. https://doi.org/10.1080/00498254.2017.1354138
Uehara S, et al. Marmoset Pulmonary Cytochrome P450 2F1 Oxidizes Biphenyl and 7-ethoxycoumarin and Hepatic Human P450 Substrates. Xenobiotica. 2018;48(7):656-662. PubMed PMID: 28689458.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Marmoset pulmonary cytochrome P450 2F1 oxidizes biphenyl and 7-ethoxycoumarin and hepatic human P450 substrates. AU - Uehara,Shotaro, AU - Uno,Yasuhiro, AU - Oshio,Toru, AU - Inoue,Takashi, AU - Sasaki,Erika, AU - Yamazaki,Hiroshi, Y1 - 2017/07/24/ PY - 2017/7/12/pubmed PY - 2018/9/25/medline PY - 2017/7/11/entrez KW - CYP2F1 KW - Common marmoset KW - drug oxidation SP - 656 EP - 662 JF - Xenobiotica; the fate of foreign compounds in biological systems JO - Xenobiotica VL - 48 IS - 7 N2 - 1. A potentially useful animal model for preclinical studies is the common marmoset (Callithrix jacchus). In this study, using reverse-transcription polymerase chain reaction from marmoset livers, we identified a novel cytochrome P450 (P450) 2F1 cDNA with an open reading frame of 1473 bp. 2. High sequence identities of 92-94% with primate P450 2 F amino acid sequences were indicated by deduced amino acid sequences of P450 2F1 cDNA. Phylogenetic analysis indicates that marmoset P450 2F1 is more congruent with primate P450 2 F forms than those of other species such as rodents. 3. Among five tissue types examined, abundant expression of marmoset P450 2F1 mRNA and P450 2F1 protein in lungs was shown. Cynomolgus monkey P450 2F1 mRNA was abundantly expressed in lungs as well as testes and ovaries in 10 tissue types. 4. Similar to those of humans and cynomolgus monkeys, marmoset P450 2F1 heterologously expressed in Escherichia coli membranes efficiently catalyzed 7-ethoxycoumarin O-deethylation and biphenyl hydroxylation, however unlike human P450 2F1, marmoset P450 2F1 exhibited hydroxylation activity toward coumarin and chlorzoxazone. 5. These findings indicated that P450 2F1 enzyme expressed in marmoset lungs and also catalyzed metabolism of xenobiotics, suggesting the importance of P450 2 F-dependent drug metabolism in marmoset lungs. SN - 1366-5928 UR - https://www.unboundmedicine.com/medline/citation/28689458/Marmoset_pulmonary_cytochrome_P450_2F1_oxidizes_biphenyl_and_7_ethoxycoumarin_and_hepatic_human_P450_substrates_ L2 - https://www.tandfonline.com/doi/full/10.1080/00498254.2017.1354138 DB - PRIME DP - Unbound Medicine ER -