On the mechanism of bile acid inhibition of rat sterol 12alpha-hydroxylase gene (CYP8B1) transcription: roles of alpha-fetoprotein transcription factor and hepatocyte nuclear factor 4alpha.

On the mechanism of bile acid inhibition of rat sterol 12alpha-hydroxylase gene (CYP8B1) transcription: roles of alpha-fetoprotein transcription factor and hepatocyte nuclear factor 4alpha.

Yang Yizeng; Zhang Ming; Eggertsen Gosta; Chiang John Y L

Biochimica et biophysica acta

2002

2002-06

The sterol 12alpha-hydroxylase (CYP8B1) is a key enzyme of the bile acid biosynthetic pathway. It regulates the composition of bile acids in bile, i.e. ratio between cholic acid (CA) and chenodeoxycholic acid (CDCA). In similarity with cholesterol 7alpha-hydroxylase (CYP7A1), this enzyme is subjected to a negative feedback regulation by bile acids. It has been recently reported that bile acid-activated farnesoid X receptor (FXR) induces the small heterodimer partner (SHP) that interacts with alpha-fetoprotein transcription factor (FTF) and down-regulates CYP7A1 transcription. We studied whether the same mechanism also regulated rat CYP8B1 gene transcription. Feeding rats with CDCA caused a

Animals; Rats; Gene Expression Regulation; Base Sequence; Cattle; Cytochrome P-450 Enzyme System/*genetics; Hepatocyte Nuclear Factor 4; *DNA-Binding Proteins; Bile Acids and Salts/*pharmacology; Steroid Hydroxylases/*genetics; alpha-Fetoproteins/genetics/*physiology; DNA; Phosphoproteins/genetics/*physiology; Steroid 12-alpha-Hydroxylase; Transcription Factors/genetics/*physiology; Sprague-Dawley; RNA; Transcription; Genetic; Promoter Regions; Messenger/genetics; Enzymologic/*drug effects/physiology; Genetic/*drug effects

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