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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

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...

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Autores principales: NISHIYAMA, Yoshihiro, NAKAYAMA, Shouta M.M., WATANABE, Kensuke P., KAWAI, Yusuke K., OHNO, Marumi, IKENAKA, Yoshinori, ISHIZUKA, Mayumi
Formato: Online Artículo Texto
Lenguaje:English
Publicado: The Japanese Society of Veterinary Science 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4873860/
https://www.ncbi.nlm.nih.gov/pubmed/26806536
http://dx.doi.org/10.1292/jvms.15-0299
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author NISHIYAMA, Yoshihiro
NAKAYAMA, Shouta M.M.
WATANABE, Kensuke P.
KAWAI, Yusuke K.
OHNO, Marumi
IKENAKA, Yoshinori
ISHIZUKA, Mayumi
author_facet NISHIYAMA, Yoshihiro
NAKAYAMA, Shouta M.M.
WATANABE, Kensuke P.
KAWAI, Yusuke K.
OHNO, Marumi
IKENAKA, Yoshinori
ISHIZUKA, Mayumi
author_sort NISHIYAMA, Yoshihiro
collection PubMed
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.
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spelling pubmed-48738602016-05-25 Strain differences in cytochrome P450 mRNA and protein expression, and enzymatic activity among Sprague Dawley, Wistar, Brown Norway and Dark Agouti rats NISHIYAMA, Yoshihiro NAKAYAMA, Shouta M.M. WATANABE, Kensuke P. KAWAI, Yusuke K. OHNO, Marumi IKENAKA, Yoshinori ISHIZUKA, Mayumi J Vet Med Sci Toxicology 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. The Japanese Society of Veterinary Science 2016-01-22 2016-04 /pmc/articles/PMC4873860/ /pubmed/26806536 http://dx.doi.org/10.1292/jvms.15-0299 Text en ©2016 The Japanese Society of Veterinary Science http://creativecommons.org/licenses/by-nc-nd/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution Non-Commercial No Derivatives (by-nc-nd) License.
spellingShingle Toxicology
NISHIYAMA, Yoshihiro
NAKAYAMA, Shouta M.M.
WATANABE, Kensuke P.
KAWAI, Yusuke K.
OHNO, Marumi
IKENAKA, Yoshinori
ISHIZUKA, Mayumi
Strain differences in cytochrome P450 mRNA and protein expression, and enzymatic activity among Sprague Dawley, Wistar, Brown Norway and Dark Agouti rats
title Strain differences in cytochrome P450 mRNA and protein expression, and enzymatic activity among Sprague Dawley, Wistar, Brown Norway and Dark Agouti rats
title_full Strain differences in cytochrome P450 mRNA and protein expression, and enzymatic activity among Sprague Dawley, Wistar, Brown Norway and Dark Agouti rats
title_fullStr Strain differences in cytochrome P450 mRNA and protein expression, and enzymatic activity among Sprague Dawley, Wistar, Brown Norway and Dark Agouti rats
title_full_unstemmed Strain differences in cytochrome P450 mRNA and protein expression, and enzymatic activity among Sprague Dawley, Wistar, Brown Norway and Dark Agouti rats
title_short Strain differences in cytochrome P450 mRNA and protein expression, and enzymatic activity among Sprague Dawley, Wistar, Brown Norway and Dark Agouti rats
title_sort strain differences in cytochrome p450 mrna and protein expression, and enzymatic activity among sprague dawley, wistar, brown norway and dark agouti rats
topic Toxicology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4873860/
https://www.ncbi.nlm.nih.gov/pubmed/26806536
http://dx.doi.org/10.1292/jvms.15-0299
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