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Hokkaido University Collection of Scholarly and Academic Papers >
Graduate School of Veterinary Medicine / Faculty of Veterinary Medicine >
Peer-reviewed Journal Articles, etc >
Strain differences in cytochrome P450 mRNA and protein expression, and enzymatic activity among Sprague Dawley, Wistar, Brown Norway and Dark Agouti rats
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| Title: | Strain differences in cytochrome P450 mRNA and protein expression, and enzymatic activity among Sprague Dawley, Wistar, Brown Norway and Dark Agouti rats |
| Authors: | Nishiyama, Yoshihiro Browse this author | | Nakayama, Shouta M. M. Browse this author →KAKEN DB | | Watanabe, Kensuke P. Browse this author | | Kawai, Yusuke K. Browse this author | | Ohno, Marumi Browse this author | | Ikenaka, Yoshinori Browse this author →KAKEN DB | | Ishizuka, Mayumi Browse this author →KAKEN DB |
| Keywords: | cytochrome P450 | | metabolism | | Rattus norvegicus | | regulation | | strain difference |
| Issue Date: | Apr-2016 |
| Publisher: | 公益社団法人 日本獣医学会 |
| Journal Title: | Journal of Veterinary Medical Science |
| Volume: | 78 |
| Issue: | 4 |
| Start Page: | 675 |
| End Page: | 680 |
| Publisher DOI: | 10.1292/jvms.15-0299 |
| Abstract: | Rat cytochrome P450 (CYP) exhibits inter-strain differences, but their analysis has been scattered across studies under different conditions. To identify these strain differences in CYP more comprehensively, mRNA expression, protein expression and metabolic activity among Wistar (WI), Sprague Dawley (SD), Dark Agouti (DA) and Brown Norway (BN) rats were compared. The mRNA level and enzymatic activity of CYP1A1 were highest in SD rats. The rank order of Cyp3a2 mRNA expression mirrored its protein expression, i.e., DA>BN>SD>WI, and was similar to the CYP3A2-dependent warfarin metabolic activity, i.e., DA>SD>BN>WI. These results suggest that the strain differences in CYP3A2 enzymatic activity are caused by differences in mRNA expression. Cyp2b1 mRNA levels, which were higher in DA rats, did not correlate with its protein expression or enzymatic activity. This suggests that the strain differences in enzymatic activity are not related to Cyp2b1 mRNA expression. In conclusion, WI rats tended to have the lowest CYP1A1, 2B1 and 3A2 mRNA expression, protein expression and enzymatic activity among the strains. In addition, SD rats had the highest CYP1A1 mRNA expression and activity, while DA rats had higher CYP2B1 and CYP3A2 mRNA and protein expression. These inter-strain differences in CYP could influence pharmacokinetic considerations in preclinical toxicological studies. |
| Rights: | https://creativecommons.org/licenses/by-nc-nd/4.0/ |
| Type: | article |
| URI: | http://hdl.handle.net/2115/62356 |
| Appears in Collections: | 獣医学院・獣医学研究院 (Graduate School of Veterinary Medicine / Faculty of Veterinary Medicine) > 雑誌発表論文等 (Peer-reviewed Journal Articles, etc)
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Submitter: 石塚 真由美
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