文章基本信息

标题：Cholesterol 25-hydroxylation activity of CYP3A
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作者：Akira Honda ; Teruo Miyazaki ; Tadashi Ikegami 等
期刊名称：JLR Papers In Press
印刷版ISSN：0022-2275
电子版ISSN：1539-7262
出版年度：2011
卷号：52
期号：8
页码：1509-1516
DOI：10.1194/jlr.M014084
语种：English
出版社：American Society for Biochemistry and Molecular Biology
摘要：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 S -hydroxycholesterol. These results demonstrate the significance of CYP3A on the production of 25-hydroxycholesterol.
关键词：cerebrotendinous xanthomatosis ; cholesterol 25-hydroxylase ; CYP3A4 ; CYP27A1 ; CYP46A1 ; 4β-hydroxycholesterol ; 25-hydroxycholesterol ; oxysterols