Regulation of cholesterol 7 alpha-hydroxylase in the liver. Purification of cholesterol 7 alpha-hydroxylase and the immunochemical evidence for the induction of cholesterol 7 alpha-hydroxylase by cholestyramine and circadian rhythm.
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Two cholesterol 7 alpha-hydroxylase isozymes were purified from liver microsomes of cholestyramine-treated female rats by using anion exchange high performance liquid chromatography. These two cytochrome P-450 isozymes were similar in electrophoretic mobility, immunocross-reactivity, and Vmax but differed in Km for cholesterol, turnover number, and charges. Antibody against the major isozyme was raised in rabbit. This antibody specifically inhibited microsomal cholesterol 7 alpha-hydroxylase activity. Immunoblot of microsomal polypeptides indicated that microsomal cholesterol 7 alpha-hydroxylase enzyme levels were increased in parallel with cholesterol 7 alpha-hydroxylase activity upon the treatment of rats with diet supplemented with cholestyramine. Both cholesterol 7 alpha-hydroxylase activity and enzyme levels were drastically reduced immediately after the removal of cholestyramine from the diet. Cholesterol 7 alpha-hydroxylase activity was also detected in the microsomes of kidney, heart, and lung in about 7-27% of the level found in the liver. 3-Methylcholanthrene treatment induced cholesterol 7 alpha-hydroxylase activity and enzyme level. In contrast, pregnenolone-16 alpha-carbonitrile or dexamethasone treatment greatly depressed enzyme and activity in rats. Cholesterol 7 alpha-hydroxylase enzyme level was 2-3-fold higher in liver microsomes of rats maintained under the reversed light cycle than under the normal light cycle. In genetically obese Zucker rats, cholesterol…
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CHR-fed WT and CarKO mice exhibit elevated mRNA levels of BA synthesis genes and reduced expression of BA export and detoxification genes compared with chow-fed mice, to compensate for a reduced BA pool.
“To compensate for a reduced BA pool,5,39,40 we observed that CHR-fed WT and CarKO mice exhibited elevated mRNA levels of BA synthesis genes and reduced expression of BA export and detoxification genes compared with chow-fed mice (Figure 10A–C).”
From Constitutive Androstane Receptor Regulates Bile Acid Homeostasis and Metabolism During Liver Regeneration (2026) · cites this paper as [39]
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- Authors
- Chiang, J. Y., Miller, W. F., & Lin, G. M.
- Affiliations
- Northeast Ohio Medical University (US)
- ORCID
- Chiang, J Y
- Venue
- Journal of Biological Chemistry
- Publisher
- Elsevier BV
- Published
- 1990-03
- Volume
- 265
- Issue
- 7
- Pages
- 3889-3897
- ISSN
- 0021-9258 (ISSN-L)
- OpenAlex
- W1531547191
- Cited by
- 123
- References
- 33
- Citations by year
- 2026: 1 · 2024: 1 · 2023: 3 · 2020: 2 · 2017: 1 · 2015: 3 · 2014: 1 · 2012: 1
- FWCI
- 19.94
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Journal of Biological Chemistry (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health (5r01gm031584-14)
- National Institute of General Medical Sciences (GM 31584)
- National Institute of Diabetes and Digestive and Kidney Diseases (R01-DK-044442)
- Topics
- Health Sciences › Medicine › Surgery › Cholesterol and Lipid Metabolism
- Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Pharmacology › Pharmacogenetics and Drug Metabolism
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Steroid Chemistry and Biochemistry
- Keywords
- CYP7A1, cytochrome P450 isozymes, enzyme induction, cholestyramine, circadian rhythm, 3-methylcholanthrene, pregnenolone-16α-carbonitrile, dexamethasone, liver microsomes, enzyme purification, antibody inhibition, obesity, Zucker rats, Western blot
- MeSH terms
- Animals, Cholesterol 7-alpha-Hydroxylase, Cholestyramine Resin, Chromatography, Chromatography, Ion Exchange, Circadian Rhythm, Enzyme Induction, Hydroxyapatites, Isoenzymes, Kinetics, Microsomes, Liver, Obesity, Organ Specificity, Polyethylene Glycols, Rats, Inbred Strains, Rats, Zucker, Steroid Hydroxylases, Durapatite, Rats
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