title: Identification of a novel sulfonated oxysterol, 5-cholesten-3beta,25-diol 3-sulfonate, in hepatocyte nuclei and mitochondria.
abstract: This study reports the discovery of a novel sulfonated oxysterol found at high levels in the mitochondria and nuclei of primary rat hepatocytes after overexpression of the gene encoding steroidogenic acute regulatory protein (StarD1). Forty-eight hours after infection of primary rat hepatocytes with recombinant adenovirus encoding StarD1, rates of bile acid synthesis increased by 4-fold. Concurrently, [(14)C]cholesterol metabolites (oxysterols) were increased dramatically in both the mitochondria and nuclei of StarD1-overexpressing cells, but not in culture medium. A water-soluble [(14)C]oxysterol product was isolated and purified by chemical extraction and reverse-phase HPLC. Enzymatic digestion, HPLC, and tandem mass spectrometry analysis identified the water-soluble oxysterol as 5-cholesten-3beta,25-diol 3-sulfonate. Further experiments detected this cholesterol metabolite in the nuclei of normal human liver tissues. Based upon these observations, we hypothesized a new pathway by which cholesterol is metabolized in the mitochondrion.
authors.affiliation: Department of Medicine, Medical College of Virginia at Virginia Commonwealth University, Richmond, 23298, USA.
authors.forename: Shunlin
authors.initials: S
authors.lastname: Ren
authors.forename: Phillip
authors.initials: P
authors.lastname: Hylemon
authors.forename: Zong-Ping
authors.initials: ZP
authors.lastname: Zhang
authors.forename: Daniel
authors.initials: D
authors.lastname: Rodriguez-Agudo
authors.forename: Dalila
authors.initials: D
authors.lastname: Marques
authors.forename: Xiaobo
authors.initials: X
authors.lastname: Li
authors.forename: Huiping
authors.initials: H
authors.lastname: Zhou
authors.forename: Gregorio
authors.initials: G
authors.lastname: Gil
authors.forename: William M
authors.initials: WM
authors.lastname: Pandak
mesh_terms: D000818:Animals; D002467:Cell Nucleus / Q000737:chemistry; D002478:Cells, Cultured; D002784:Cholesterol / Q000378:metabolism; D002790:Cholesterol 7-alpha-Hydroxylase / Q000096:biosynthesis; D002851:Chromatography, High Pressure Liquid; D002853:Chromatography, Liquid / Q000379:methods; D022781:Hepatocytes / Q000737:chemistry*; D006801:Humans; D006888:Hydroxycholesterols / Q000032:analysis*; D013058:Mass Spectrometry / Q000379:methods; D008930:Mitochondria, Liver / Q000737:chemistry; D010750:Phosphoproteins / Q000096:biosynthesis; D051381:Rats; D013463:Sulfuric Acid Esters / Q000032:analysis*; D000098682:Steroidogenic Acute Regulatory Protein
chemical_list: C511951:5-cholesten-3,25-diol 3-sulfonate; D006888:Hydroxycholesterols; D010750:Phosphoproteins; D013463:Sulfuric Acid Esters; D000098682:Steroidogenic Acute Regulatory Protein; D002784:Cholesterol; D002790:Cholesterol 7-alpha-Hydroxylase