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Investigation of the CYP2C9 induction profile in human hepatocytes by combining experimental and modelling approachesBelič, Aleš ...The goal of the present review is to characterise the induction profile of CYP2C9, a member of the cytochrome P450 superfamily. Since the mechanism of CYP2C9 induction is fairly complex, with ... parallel processes triggered by various inducers, an evaluation of the experimental results is often a great challenge. At least three nuclear receptors, the glucocrticoid receptor (GR), the pregnane X receptor (PXR) and the constitutive androstane receptor (CAR), are known to mediate the CYP2C9 gene induction in man. However, mathematical modelling and simulation can provide an appropriate tool for the interpretation of CYP2C9 regulatory mechanisms. As an example, we present modelling and simulation approaches of the CYP2C9 gene expression in human hepatocytes treated with well-known CYP2C9 inducersČ the steroid hormone precursor dehydroepiandrosterone (DHEA) and the synthetic glucocorticoid dexamethasone (DXM). The results of the analysis suggest that in addition to the potent function of GR and the further involvement of PXR and CAR activatedby DXM or DHEA, an additional factor might play a role in CYP2C9 regulation by DHEA. The novel potential candidate for DHEA action in CYP2C9 induction is likely to be the estrogen receptor. Additionally, the balance of DHEA sulphation-desulphation processes should also be considered in any description of DHEA-induced CYP2C9 profiles.Source: Current drug metabolism. - ISSN 1389-2002 (Vol. 10, no. 10, Dec. 2009, str. 1066-1074)Type of material - article, component partPublish date - 2009Language - englishCOBISS.SI-ID - 7564372
Author
Belič, Aleš |
Temesvári, Manna |
Kohalmy, K. |
Vrzal, Radim |
Dvorak, Zdenek |
Rozman, Damjana, 1960- |
Monostory, Katalin
Topics
CYP2C9 |
estrogenski receptor |
dehidroepiandrosteron |
deksametazon |
matematično modeliranje |
matematično modeliranje |
CYP2C9 |
estrogen receptor |
dehydroepiandrosterone |
dexamethasone |
mathematical modelling
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Database name | Field | Year |
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Belič, Aleš | 15395 |
Temesvári, Manna | |
Kohalmy, K. | |
Vrzal, Radim | |
Dvorak, Zdenek | |
Rozman, Damjana, 1960- | 06013 |
Monostory, Katalin |
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