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Age-associated changes of cytochrome P450 and related phase-2 gene/proteins in livers of rats

Cytochrome P450s (CYPs) are phase-I metabolic enzymes playing important roles in drug metabolism, dietary chemicals and endogenous molecules. Age is a key factor influencing P450s expression. Thus, age-related changes of CYP 1–4 families and bile acid homeostasis-related CYPs, the corresponding nucl...

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Autores principales: Xu, Shang-Fu, Hu, An-Ling, Xie, Lu, Liu, Jia-Jia, Wu, Qin, Liu, Jie
Formato: Online Artículo Texto
Lenguaje:English
Publicado: PeerJ Inc. 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6681801/
https://www.ncbi.nlm.nih.gov/pubmed/31396457
http://dx.doi.org/10.7717/peerj.7429
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author Xu, Shang-Fu
Hu, An-Ling
Xie, Lu
Liu, Jia-Jia
Wu, Qin
Liu, Jie
author_facet Xu, Shang-Fu
Hu, An-Ling
Xie, Lu
Liu, Jia-Jia
Wu, Qin
Liu, Jie
author_sort Xu, Shang-Fu
collection PubMed
description Cytochrome P450s (CYPs) are phase-I metabolic enzymes playing important roles in drug metabolism, dietary chemicals and endogenous molecules. Age is a key factor influencing P450s expression. Thus, age-related changes of CYP 1–4 families and bile acid homeostasis-related CYPs, the corresponding nuclear receptors and a few phase-II genes were examined. Livers from male Sprague-Dawley rats at fetus (−2 d), neonates (1, 7, and 14 d), weanling (21 d), puberty (28 and 35 d), adulthood (60 and 180 d), and aging (540 and 800 d) were collected and subjected to qPCR analysis. Liver proteins from 14, 28, 60, 180, 540 and 800 days of age were also extracted for selected protein analysis by western blot. In general, there were three patterns of their expression: Some of the drug-metabolizing enzymes and related nuclear receptors were low in fetal and neonatal stage, increased with liver maturation and decreased quickly at aging (AhR, Cyp1a1, Cyp2b1, Cyp2b2, Cyp3a1, Cyp3a2, Ugt1a2); the majority of P450s (Cyp1a2, Cyp2c6, Cyp2c11, Cyp2d2, Cyp2e1, CAR, PXR, FXR, Cyp7a1, Cyp7b1. Cyp8b1, Cyp27a1, Ugt1a1, Sult1a1, Sult1a2) maintained relatively high levels throughout the adulthood, and decreased at 800 days of age; and some had an early peak between 7 and 14 days (CAR, PXR, PPARα, Cyp4a1, Ugt1a2). The protein expression of CYP1A2, CYP2B1, CYP2E1, CYP3A1, CYP4A1, and CYP7A1 corresponded the trend of mRNA changes. In summary, this study characterized three expression patterns of 16 CYPs, five nuclear receptors, and four phase-II genes during development and aging in rat liver, adding to our understanding of age-related CYP expression changes and age-related disorders.
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spelling pubmed-66818012019-08-08 Age-associated changes of cytochrome P450 and related phase-2 gene/proteins in livers of rats Xu, Shang-Fu Hu, An-Ling Xie, Lu Liu, Jia-Jia Wu, Qin Liu, Jie PeerJ Biochemistry Cytochrome P450s (CYPs) are phase-I metabolic enzymes playing important roles in drug metabolism, dietary chemicals and endogenous molecules. Age is a key factor influencing P450s expression. Thus, age-related changes of CYP 1–4 families and bile acid homeostasis-related CYPs, the corresponding nuclear receptors and a few phase-II genes were examined. Livers from male Sprague-Dawley rats at fetus (−2 d), neonates (1, 7, and 14 d), weanling (21 d), puberty (28 and 35 d), adulthood (60 and 180 d), and aging (540 and 800 d) were collected and subjected to qPCR analysis. Liver proteins from 14, 28, 60, 180, 540 and 800 days of age were also extracted for selected protein analysis by western blot. In general, there were three patterns of their expression: Some of the drug-metabolizing enzymes and related nuclear receptors were low in fetal and neonatal stage, increased with liver maturation and decreased quickly at aging (AhR, Cyp1a1, Cyp2b1, Cyp2b2, Cyp3a1, Cyp3a2, Ugt1a2); the majority of P450s (Cyp1a2, Cyp2c6, Cyp2c11, Cyp2d2, Cyp2e1, CAR, PXR, FXR, Cyp7a1, Cyp7b1. Cyp8b1, Cyp27a1, Ugt1a1, Sult1a1, Sult1a2) maintained relatively high levels throughout the adulthood, and decreased at 800 days of age; and some had an early peak between 7 and 14 days (CAR, PXR, PPARα, Cyp4a1, Ugt1a2). The protein expression of CYP1A2, CYP2B1, CYP2E1, CYP3A1, CYP4A1, and CYP7A1 corresponded the trend of mRNA changes. In summary, this study characterized three expression patterns of 16 CYPs, five nuclear receptors, and four phase-II genes during development and aging in rat liver, adding to our understanding of age-related CYP expression changes and age-related disorders. PeerJ Inc. 2019-08-02 /pmc/articles/PMC6681801/ /pubmed/31396457 http://dx.doi.org/10.7717/peerj.7429 Text en ©2019 Xu et al. https://creativecommons.org/licenses/by/4.0/ This is an open access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, reproduction and adaptation in any medium and for any purpose provided that it is properly attributed. For attribution, the original author(s), title, publication source (PeerJ) and either DOI or URL of the article must be cited.
spellingShingle Biochemistry
Xu, Shang-Fu
Hu, An-Ling
Xie, Lu
Liu, Jia-Jia
Wu, Qin
Liu, Jie
Age-associated changes of cytochrome P450 and related phase-2 gene/proteins in livers of rats
title Age-associated changes of cytochrome P450 and related phase-2 gene/proteins in livers of rats
title_full Age-associated changes of cytochrome P450 and related phase-2 gene/proteins in livers of rats
title_fullStr Age-associated changes of cytochrome P450 and related phase-2 gene/proteins in livers of rats
title_full_unstemmed Age-associated changes of cytochrome P450 and related phase-2 gene/proteins in livers of rats
title_short Age-associated changes of cytochrome P450 and related phase-2 gene/proteins in livers of rats
title_sort age-associated changes of cytochrome p450 and related phase-2 gene/proteins in livers of rats
topic Biochemistry
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6681801/
https://www.ncbi.nlm.nih.gov/pubmed/31396457
http://dx.doi.org/10.7717/peerj.7429
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