REGULATION OF CHOLESTEROL 7-ALPHA-HYDROXYLASE MESSENGER-RNA AND TRANSCRIPTIONAL ACTIVITY BY TAUROCHOLATE AND CHOLESTEROL IN THE CHRONIC BILIARY DIVERTED RAT

Title

REGULATION OF CHOLESTEROL 7-ALPHA-HYDROXYLASE MESSENGER-RNA AND TRANSCRIPTIONAL ACTIVITY BY TAUROCHOLATE AND CHOLESTEROL IN THE CHRONIC BILIARY DIVERTED RAT

Creator

Pandak W M; Li Y C; Chiang J Y L; Studer E J; Gurley E C; Heuman D M; Vlahcevic Z R; Hylemon P B

Publisher

Journal of Biological Chemistry

Date

1991
1991-02

Description

Cholesterol 7-alpha-hydroxylase catalyzes the rate-limiting step in the bile acid biosynthetic pathway. Regulation of this pathway is thought to occur solely as a result of a negative feedback control mechanism that is dependent upon the flux and composition of bile salts undergoing enterohepatic circulation. We have used the chronic biliary diverted (CBD) rat model to study the mechanism of regulation of cholesterol 7-alpha-hydroxylase by taurocholate. As compared to nonoperated controls, CBD rats exhibited a 4.2-fold increase in cholesterol 7-alpha-hydroxylase-specific activity, a 4.5-fold increase in enzyme mass, a 10-fold increase in steady-state mRNA levels, and a 3.4-fold increase in transcriptional (nuclear "run-on") activity. Intraduodenal infusion of taurocholate at a rate of 36-mu-mol/100 g/h for 48 h in CBD rats caused a significant (p < 0.05) decrease (64%) in cholesterol 7-alpha-hydroxylase-specific activity, mass (72%), steady-state mRNA levels (74%), and transcriptional activity (57%) as compared to CBD controls. Cholesterol feeding increased cholesterol 7-alpha-hydroxylase-specific activity (288%), poly(A) RNA levels (291%), and transcriptional activity (220%) as compared to control animals. These results provide convincing evidence that bile salts, either directly or indirectly, down-regulate in vivo transcription of the cholesterol 7-alpha-hydroxylase gene, which is probably the major mechanism regulating the levels of this enzyme. The results of this study also suggest that the promoter for cholesterol 7-alpha-hydroxylase may have both bile salt- and sterol-responsive elements.

Subject

7-alpha-hydroxylase; bile-acid synthesis; Biochemistry & Molecular Biology; biosynthesis; coa reductase; Enzymes; hepatocytes; liver microsomes; metabolism; substrate

Identifier

n/a

Format

Journal Article

URL Address

n/a

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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

3416-3421

Issue

6

Volume

266

Citation

Pandak W M; Li Y C; Chiang J Y L; Studer E J; Gurley E C; Heuman D M; Vlahcevic Z R; Hylemon P B, “REGULATION OF CHOLESTEROL 7-ALPHA-HYDROXYLASE MESSENGER-RNA AND TRANSCRIPTIONAL ACTIVITY BY TAUROCHOLATE AND CHOLESTEROL IN THE CHRONIC BILIARY DIVERTED RAT,” NEOMED Bibliography Database, accessed May 18, 2021, https://neomed.omeka.net/items/show/7758.

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