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Cited by 193

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Regulation of cholesterol 7 alpha-hydroxylase mRNA and transcriptional activity by taurocholate and cholesterol in the chronic biliary diverted rat

Open access
Pandak, W M, Li, Y C, Chiang, J Y, Studer, E J, Gurley, E C, Heuman, D M, Vlahcevic, Z R, Hylemon, P B·1991·Journal of Biological Chemistry

Abstract

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 mumol/100 g/h for 48 h in CBD rats caused a significant (p less than 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.

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Metadata

Authors
Pandak, W. M., Li, Y. C., Chiang, J. Y., Studer, E. J., Gurley, E. C., Heuman, D. M., Vlahcevic, Z. R., & Hylemon, P. B.
Venue
Journal of Biological Chemistry
Publisher
Elsevier BV
Published
1991-02
Volume
266
Issue
6
Pages
3416-3421
ISSN
0021-9258 (ISSN-L)
OpenAlex
W1600065401
Cited by
193
References
1
FWCI
23.44
Type
journal article
Language
en
Open access
hybrid

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CoChat. (2026). Citation check: Regulation of cholesterol 7 alpha-hydroxylase mRNA and transcriptional activity by taurocholate and cholesterol in the chronic biliary diverted rat. https://app.cochat.ai/papers/10.1016/s0021-9258(19)67810-5
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Pandak, W. M., Li, Y. C., Chiang, J. Y., Studer, E. J., Gurley, E. C., Heuman, D. M., Vlahcevic, Z. R., & Hylemon, P. B. (1991). Regulation of cholesterol 7 alpha-hydroxylase mRNA and transcriptional activity by taurocholate and cholesterol in the chronic biliary diverted rat. Journal of Biological Chemistry. https://doi.org/10.1016/s0021-9258(19)67810-5

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