TY - JOUR
T1 - Higher expression of cytochrome P450 3A4 in human mesenchymal and adipose-derived stem cells than in dermal fibroblasts
T2 - With emphasis on the correlation with basal pregnane X receptor expression
AU - Chiang, Tsai Shin
AU - Yang, Kai Chiang
AU - Wu, Yao Ming
AU - Lai, Hong Shiee
AU - Jiang, Ching Chuan
AU - Chiou, Ling Ling
AU - Lee, Kuang Lun
AU - Huang, Guan Tarn
AU - Lee, Hsuan Shu
N1 - Publisher Copyright:
© 2014 Elsevier B.V. All rights reserved.
PY - 2014/11
Y1 - 2014/11
N2 - Among the cytochrome P 450 (CYP) enzymes, CYP3A4 is most abundantly existed and metabolizes most of the drugs. We have shown human dermal fibroblasts (HDFs) express low levels of CYPs, but could be engineered to express much higher levels to be used as drug metabolism prediction. To seek better cell source for engineering, the basal mRNA expression and enzyme activities of CYP3A4 in HDFs (n = 5), bone marrow-derived mesenchymal stem cells (BMMSCs, n = 7), and adipose-derived stem cells (ADSCs, n = 3) were compared. The basal CYP3A4 expression and activity in BMMSCs and ADSCs were significantly higher than in HDFs. However, the coefficient of variation of CYP3A4 expression was very high in each cell type. Comparing the expression levels of 4 regulators glucocorticoid receptor, pregnane X receptor (PXR), hepatocyte nuclear factor 4α, and hydrocarbon receptor nuclear translocator in the total 15 cell samples, we found the only basal PXR expression was significantly correlated with CYP3A4 expression. The gender and age of patients were not significant determinants in the expressions of PXR and CYP3A4. In conclusion, BMMSCs and ADSCs expressed higher levels of CYP3A4 than HDFs and the expression of CYP3A4 might be mainly determined by basal PXR expression.
AB - Among the cytochrome P 450 (CYP) enzymes, CYP3A4 is most abundantly existed and metabolizes most of the drugs. We have shown human dermal fibroblasts (HDFs) express low levels of CYPs, but could be engineered to express much higher levels to be used as drug metabolism prediction. To seek better cell source for engineering, the basal mRNA expression and enzyme activities of CYP3A4 in HDFs (n = 5), bone marrow-derived mesenchymal stem cells (BMMSCs, n = 7), and adipose-derived stem cells (ADSCs, n = 3) were compared. The basal CYP3A4 expression and activity in BMMSCs and ADSCs were significantly higher than in HDFs. However, the coefficient of variation of CYP3A4 expression was very high in each cell type. Comparing the expression levels of 4 regulators glucocorticoid receptor, pregnane X receptor (PXR), hepatocyte nuclear factor 4α, and hydrocarbon receptor nuclear translocator in the total 15 cell samples, we found the only basal PXR expression was significantly correlated with CYP3A4 expression. The gender and age of patients were not significant determinants in the expressions of PXR and CYP3A4. In conclusion, BMMSCs and ADSCs expressed higher levels of CYP3A4 than HDFs and the expression of CYP3A4 might be mainly determined by basal PXR expression.
KW - Adipose-derived stem cells
KW - Bone marrow-derived mesenchymal stem cells
KW - Cytochrome
KW - Human dermal fibroblasts
KW - P450 3A4
KW - Pregnane
KW - X receptor
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U2 - 10.1016/j.procbio.2014.08.006
DO - 10.1016/j.procbio.2014.08.006
M3 - Article
AN - SCOPUS:84908328469
SN - 1359-5113
VL - 49
SP - 1983
EP - 1989
JO - Process Biochemistry
JF - Process Biochemistry
IS - 11
ER -