Mechanisms of cholesterol and sterol regulatory element binding protein regulation of the sterol 12 alpha-hydroxylase gene (CYP8B1)

Title

Mechanisms of cholesterol and sterol regulatory element binding protein regulation of the sterol 12 alpha-hydroxylase gene (CYP8B1)

Creator

Yang Y Z; Eggertsen G; Gafvels M; Andersson U; Einarsson C; Bjorkhem I; Chiang J Y L

Publisher

Biochemical and Biophysical Research Communications

Date

2004
2004-08

Description

Sterol 12alpha-hydroxylase (CYP8B1) is an obligatory enzyme for the synthesis of cholic acid and regulation of liver bile acid synthesis and intestine cholesterol absorption. The present study evaluates the roles for sterol regulatory element binding proteins (SREBPs) in the regulation of the CYP8B1 gene. Cholesterol feeding of mice and rats decreased the activity of CYP8B1, contrary to the up-regulation of cholesterol 7alpha-hydroxylase (CYP7A1). Cholesterol feeding also reduced mRNA levels for SREBP-1 but not for SREBP-2 in rat livers. Cholesterol and 25-hydroxycholesterol decreased the CYP8B1/luciferase reporter activity. Co-transfection of SREBP-1a and -1c stimulated CYP8B1 promoter activity, while SREBP-2 did not have any effects. Electrophoretic mobility shift assay and mutagenesis analyses identified several functional sterol regulatory elements (SRE) and E-box motifs in the rat CYP8B1 promoter. Our results indicate that SREBP-1a and -1c enhance transcription of the CYP8B1 gene through binding to SRE. Cholesterol loading reduces SREBP-1 mRNA expression in addition to reducing functional SREBP-1 protein, and results in decreasing CYP8B1 gene transcription. (C) 2004 Elsevier Inc. All rights reserved.

Subject

bile acids; bile-acid metabolism; Biochemistry & Molecular Biology; Biophysics; cholesterol; CYP8B1; gene regulation; liver; mice; mouse; pathway; promoter; rat; receptor lxr-alpha; SREBP; srebps; suppresses

Format

Journal Article

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Rights

Article information provided for research and reference use only. All rights are retained by the journal listed under publisher and/or the creator(s).

Pages

1204-1210

Issue

4

Volume

320

Citation

Yang Y Z; Eggertsen G; Gafvels M; Andersson U; Einarsson C; Bjorkhem I; Chiang J Y L, “Mechanisms of cholesterol and sterol regulatory element binding protein regulation of the sterol 12 alpha-hydroxylase gene (CYP8B1),” NEOMED Bibliography Database, accessed June 13, 2021, https://neomed.omeka.net/items/show/7636.

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