Role of farnesoid X receptor in establishment of ontogeny of phase-I drug metabolizing enzyme genes in mouse liver.
- Author:
Lai PENG
1
,
2
;
Stephanie PIEKOS
3
;
Grace L GUO
4
;
Xiao-Bo ZHONG
3
Author Information
1. Department of Pharmaceutical Sciences, School of Pharmacy, University of Connecticut, Storrs, CT 06269, USA
2. Key Laboratory of System Biomedicine, Center for Comparative Biomedicine, Institute of Systems Biomedicine, Shanghai Jiao Tong University, Shanghai 200240, China.
3. Department of Pharmaceutical Sciences, School of Pharmacy, University of Connecticut, Storrs, CT 06269, USA.
4. Department of Pharmacology and Toxicology, School of Pharmacy, Rutgers University, Piscataway, NJ 08854, USA.
- Publication Type:Journal Article
- Keywords:
ADH, alcohol dehydrogenase;
AKR, aldoketo reductase;
ALDH, aldehyde dehydrogenase;
CES, carboxylesterase (Ces);
DPYD, dihydropyrimidine dehydrogenase;
Drug metabolizing enzymes;
EPHX, epoxide hydrolase;
FMO, flavin monooxygenases, Farnesoid X receptor (FXR);
Farnesoid X receptor;
Fxr-null mouse;
Gene expression;
Liver;
NQO, quinone oxidoreductase;
Ontogeny;
P450, cytochrome P450;
PON, paraoxonase;
POR, cytochrome P450 oxidoreductase
- From:
Acta Pharmaceutica Sinica B
2016;6(5):453-459
- CountryChina
- Language:English
-
Abstract:
The expression of phase-I drug metabolizing enzymes in liver changes dramatically during postnatal liver maturation. Farnesoid X receptor (FXR) is critical for bile acid and lipid homeostasis in liver. However, the role of FXR in regulating ontogeny of phase-I drug metabolizing genes is not clear. Hence, we applied RNA-sequencing to quantify the developmental expression of phase-I genes in both-null and control (C57BL/6) mouse livers during development. Liver samples of male C57BL/6 and-null mice at 6 different ages from prenatal to adult were used. The-null showed an overall effect to diminish the "day-1 surge" of phase-I gene expression, including cytochrome P450s at neonatal ages. Among the 185 phase-I genes from 12 different families, 136 were expressed, and differential expression during development occurred in genes from all 12 phase-I families, including hydrolysis: carboxylesterase (), paraoxonase (), and epoxide hydrolase (); reduction: aldoketo reductase (), quinone oxidoreductase (), and dihydropyrimidine dehydrogenase (); and oxidation: alcohol dehydrogenase (), aldehyde dehydrogenase (), flavin monooxygenases (), molybdenum hydroxylase (and), cytochrome P450 (P450), and cytochrome P450 oxidoreductase (). The data also suggested new phase-I genes potentially targeted by FXR. These results revealed an important role of FXR in regulation of ontogeny of phase-I genes.
