Abstract:
:Cytochromes P450 of the liver are involved in maintenance of lipid homeostasis (cholesterol, vitamin D, oxysterol and bile acid metabolism) and in detoxification processes of endogenous compounds (i. e. bile acids) and xenochemicals (drugs). This review describes the roles of various CYPs in production of cholesterol related endogenous metabolites. These metabolites (oxysterols, bile acids, vitamin D3) act as activators of a battery of nuclear receptors, in particular liver X receptor (LXR), pregnane X receptor (PXR), constitutive androstane receptor (CAR), farnesoid X receptor (FXR) and vitamin D receptor (VDR). Nuclear receptors that are activated by cholesterol metabolites or by drugs (i. e. PXR or CAR) bind to promoter regions of responsive genes. The downstream genes include CYPs from cholesterol metabolism and/or from drug metabolism whose transcription is activated in a feedback manner. Cholesterol metabolites are thus major actors of the cross-talk that is mediated by nuclear receptors and activated CYPs. This results in a simultaneous regulation of genes from cholesterol metabolism, drug metabolism and also other pathways. The interplay between metabolism of endogenous and exogenous compounds is a frequent cause of drug failures that can now be explained at the molecular level.
journal_name
Curr Drug Metabjournal_title
Current drug metabolismauthors
Hafner M,Rezen T,Rozman Ddoi
10.2174/138920011795016890subject
Has Abstractpub_date
2011-02-01 00:00:00pages
173-85issue
2eissn
1389-2002issn
1875-5453pii
BSP/CDM/E-Pub/000126journal_volume
12pub_type
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