Cited by 123Cholesterol and Lipid MetabolismPharmacogenetics and Drug MetabolismSteroid Chemistry and Biochemistry

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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Chiang, J Y, Miller, W F, Lin, G M·1990·Journal of Biological Chemistry

Abstract

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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Crossref · 10.1016/s0021-9258(19)39677-2

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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).”

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Authors
Chiang, J. Y., Miller, W. F., & Lin, G. M.
Affiliations
Northeast Ohio Medical University (US)
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
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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