| Cholesterol 25-hydroxylation activity of CYP3A. | |
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MedLine Citation:
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PMID: 21576599 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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To date, many studies have been conducted using 25-hydroxycholesterol, which is a potent regulator of lipid metabolism. However, the origins of this oxysterol have not been entirely elucidated. Cholesterol 25-hydroxylase is one of the enzymes responsible for the metabolism of 25-hydroxycholesterol, but the expression of this enzyme is very low in humans. This oxysterol is also synthesized by sterol 27-hydroxylase (CYP27A1) and cholesterol 24-hydroxylase(CYP46A1), but it is only a minor product of these enzymes. We now report that CYP3A synthesizes a significant amount of 25-hydroxycholesterol and may participate in the regulation of lipid metabolism. Induction of CYP3A by pregnenolone-16α-carbonitrile caused the accumulation of 25-hydroxycholesterol in a cell line derived from mouse liver. Furthermore, treatment of the cells with troleandomycin, a specific inhibitor of CYP3A, significantly reduced cellular 25-hydroxycholesterol concentrations. In cells that overexpressed human recombinant CYP3A4, the activity of cholesterol 25-hydroxylation was found to be higher than that of cholesterol 4β-hydroxylation, a known marker activity of CYP3A4. In addition, 25-hydroxycholesterol concentrations in normal human sera correlated positively with the levels of 4β-hydroxycholesterol (r = 0.650, P < 0.0001, n = 78), but did not significantly correlate with the levels of 27-hydroxycholesterol or 24S-hydroxycholesterol. These results demonstrate the significance of CYP3A on the production of 25-hydroxycholesterol. |
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Authors:
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Akira Honda; Teruo Miyazaki; Tadashi Ikegami; Junichi Iwamoto; Tomomi Maeda; Takeshi Hirayama; Yoshifumi Saito; Tamio Teramoto; Yasushi Matsuzaki |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't Date: 2011-05-16 |
Journal Detail:
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Title: Journal of lipid research Volume: 52 ISSN: 0022-2275 ISO Abbreviation: J. Lipid Res. Publication Date: 2011 Aug |
Date Detail:
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Created Date: 2011-07-18 Completed Date: 2011-11-08 Revised Date: 2012-09-25 |
Medline Journal Info:
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Nlm Unique ID: 0376606 Medline TA: J Lipid Res Country: United States |
Other Details:
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Languages: eng Pagination: 1509-16 Citation Subset: IM |
Affiliation:
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Department of Gastroenterology, Center for Collaborative Research, Ibaraki 300-0395, Japan. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Animals Blotting, Western Cell Line Cytochrome P-450 CYP3A / genetics, metabolism* Cytochrome P-450 Enzyme System / antagonists & inhibitors, metabolism* Electrophoresis, Polyacrylamide Gel Enzyme Activation / drug effects* Gene Expression Hepatocytes / cytology, enzymology* Humans Hydroxycholesterols / metabolism* Lipid Metabolism / physiology* Liver / cytology, enzymology* Mice Polymerase Chain Reaction Pregnenolone Carbonitrile / pharmacology RNA, Messenger / analysis, biosynthesis Steroid Hydroxylases Troleandomycin / pharmacology |
| Chemical | |
Reg. No./Substance:
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0/Hydroxycholesterols; 0/RNA, Messenger; 1434-54-4/Pregnenolone Carbonitrile; 2140-46-7/25-hydroxycholesterol; 2751-09-9/Troleandomycin; 9035-51-2/Cytochrome P-450 Enzyme System; EC 1.14.-/Steroid Hydroxylases; EC 1.14.13.67/CYP3A4 protein, human; EC 1.14.14.1/CYP3A protein, mouse; EC 1.14.14.1/Cytochrome P-450 CYP3A; EC 1.14.99.38/cholesterol 25-hydroxylase |
| Comments/Corrections | |
Comment In:
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J Lipid Res. 2011 Aug;52(8):1447-9
[PMID:
21652732
]
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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