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标题：Identification of a novel sulfonated oxysterol, 5-cholesten-3{beta},25-diol 3-sulfonate, in hepatocyte nuclei and mitochondria
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作者：Ren, Shunlin ; Hylemon, Phillip ; Zhang, Zong-Ping 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：2006
卷号：47
期号：5
页码：1081-1090
DOI：10.1194/jlr.M600019-JLR200
出版社：American Society for Biochemistry and Molecular Biology
摘要：This study reports the discovery of a novel sulfonated oxysterolfound at high levels in the mitochondria and nuclei of primaryrat hepatocytes after overexpression of the gene encoding steroidogenicacute regulatory protein (StarD1). Forty-eight hours after infectionof primary rat hepatocytes with recombinant adenovirus encodingStarD1, rates of bile acid synthesis increased by 4-fold. Concurrently,[¹⁴C]cholesterol metabolites (oxysterols) were increased dramaticallyin both the mitochondria and nuclei of StarD1-overexpressingcells, but not in culture medium. A water-soluble [¹⁴C]oxysterolproduct was isolated and purified by chemical extraction andreverse-phase HPLC. Enzymatic digestion, HPLC, and tandem massspectrometry analysis identified the water-soluble oxysterolas 5-cholesten-3ß,25-diol 3-sulfonate. Further experimentsdetected this cholesterol metabolite in the nuclei of normalhuman liver tissues. Based upon these observations, we hypothesizeda new pathway by which cholesterol is metabolized in the mitochondrion. Supplementary key words nucleus • steroidogenic acute regulatory protein • cholesterol transporter • bile acids • cholesterol metabolism • nuclear oxysterol ligands Abbreviations: CYP27A1, cholesterol 27-hydroxylase; CYP7A1, cholesterol 7 ${alpha}$ -hydroxylase; HST2, hydroxycholesterol sulfonate transferase 2; LXR, liver sterol receptor; StarD1, steroidogenic acute regulatory protein