Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Pivot Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Target Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Query: UNIPROT:B6ZGS9 (
Farnesoid X receptor
)
212
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
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
Fxr
-null and control (C57BL/6) mouse livers during development. Liver samples of male C57BL/6 and
Fxr
-null mice at 6 different ages from prenatal to adult were used. The
Fxr
-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 (
Ces
), paraoxonase (
Pon
), and epoxide hydrolase (
Ephx
); reduction: aldoketo reductase (
Akr
), quinone oxidoreductase (
Nqo
), and dihydropyrimidine dehydrogenase (
Dpyd
); and oxidation:
alcohol dehydrogenase
(
Adh
), aldehyde dehydrogenase (
Aldh
), flavin monooxygenases (
Fmo
), molybdenum hydroxylase (
Aox
and
Xdh
), cytochrome P450 (P450), and cytochrome P450 oxidoreductase (
Por
). 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.
...
PMID:Role of farnesoid X receptor in establishment of ontogeny of phase-I drug metabolizing enzyme genes in mouse liver. 2770 14
