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Strain differences in cytochrome P450 mRNA and protein expression, and enzymatic activity among Sprague Dawley, Wistar, Brown Norway and Dark Agouti rats

Journal of Veterinary Medical Science, 2016, Vol.78(4), pp.675-680 [Peer Reviewed Journal]

2016 by the Japanese Society of Veterinary Science ;Copyright Japan Science and Technology Agency 2016 ;2016 The Japanese Society of Veterinary Science 2016 ;ISSN: 0916-7250 ;EISSN: 1347-7439 ;DOI: 10.1292/jvms.15-0299 ;PMID: 26806536

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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
Author: NISHIYAMA, Yoshihiro ; NAKAYAMA, Shouta M.M. ; WATANABE, Kensuke P. ; KAWAI, Yusuke K. ; OHNO, Marumi ; IKENAKA, Yoshinori ; ISHIZUKA, Mayumi
Subjects: Animals ; Cytochrome P-450 Enzyme System - genetics ; Cytochrome P-450 Enzyme System - metabolism ; cytochrome P450 ; Male ; metabolism ; Protein Isoforms - genetics ; Protein Isoforms - metabolism ; Rats ; Rats, Inbred BN - genetics ; Rats, Inbred BN - metabolism ; Rats, Inbred Strains - genetics ; Rats, Inbred Strains - metabolism ; Rats, Sprague-Dawley - genetics ; Rats, Sprague-Dawley - metabolism ; Rats, Wistar - genetics ; Rats, Wistar - metabolism ; Rattus norvegicus ; regulation ; RNA, Messenger - biosynthesis ; strain difference ; Toxicology ; Transcription Factors - metabolism
Is Part Of: Journal of Veterinary Medical Science, 2016, Vol.78(4), pp.675-680
Description: 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.
Publisher: Japan: JAPANESE SOCIETY OF VETERINARY SCIENCE
Language: English
Identifier: ISSN: 0916-7250
EISSN: 1347-7439
DOI: 10.1292/jvms.15-0299
PMID: 26806536
Source: MEDLINE
PubMed Central
Alma/SFX Local Collection

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Strain differences in cytochrome P450 mRNA and protein expression, and enzymatic activity among Sprague Dawley, Wistar, Brown Norway and Dark Agouti rats

2016 by the Japanese Society of Veterinary Science ;Copyright Japan Science and Technology Agency 2016 ;2016 The Japanese Society of Veterinary Science 2016 ;ISSN: 0916-7250 ;EISSN: 1347-7439 ;DOI: 10.1292/jvms.15-0299 ;PMID: 26806536

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