title: Sulfation of 25-hydroxycholesterol by SULT2B1b decreases cellular lipids via the LXR/SREBP-1c signaling pathway in human aortic endothelial cells.
abstract: OBJECTIVE
  25-Hydroxycholesterol (25HC) and its sulfated metabolite, 25-hydroxycholesterol-3-sulfate (25HC3S), regulate certain aspects of lipid metabolism in opposite ways. Hence, the enzyme for the biosynthesis of 25HC3S, oxysterol sulfotransferase (SULT2B1b), may play a crucial role in regulating lipid metabolism. We evaluate the effect of 25HC sulfation on lipid metabolism by overexpressing the gene encoding SULT2B1b in human aortic endothelial cells (HAECs) in culture.
  
  
  RESULTS
  The human SULT2B1b gene was successfully overexpressed in HAECs following infection using a recombinant adenovirus. HPLC analysis demonstrated that more than 50% of (3)H-25HC was sulfated in 24h following overexpression of the SULT2B1b gene. In the presence of 25HC, SULT2B1b overexpression significantly decreased mRNA and protein levels of LXR, ABCA1, SREBP-1c, ACC-1, and FAS, which are key regulators of lipid biosynthesis and transport; and subsequently reduced cellular lipid levels. Overexpression of the gene encoding SULT2B1b gave similar results as adding exogenous 25HC3S. However, in the absence of 25HC or in the presence of T0901317, synthetic liver oxysterol receptor (LXR) agonist, SULT2B1b overexpression had no effect on the regulation of key genes involved in lipid metabolism.
  
  
  CONCLUSIONS
  Our data indicate that sulfation of 25HC by SULT2B1b plays an important role in the maintenance of intracellular lipid homeostasis via the LXR/SREBP-1c signaling pathway in HAECs.
authors.affiliation: Department of Medicine, Virginia Commonwealth University/Veterans Affairs McGuire Medical Center, Richmond, VA 23249, United States.
authors.forename: Qianming
authors.initials: Q
authors.lastname: Bai
authors.forename: Leyuan
authors.initials: L
authors.lastname: Xu
authors.forename: Genta
authors.initials: G
authors.lastname: Kakiyama
authors.forename: Melissa Ann
authors.initials: MA
authors.lastname: Runge-Morris
authors.forename: Phillip B
authors.initials: PB
authors.lastname: Hylemon
authors.forename: Lianhua
authors.initials: L
authors.lastname: Yin
authors.forename: William M
authors.initials: WM
authors.lastname: Pandak
authors.forename: Shunlin
authors.initials: S
authors.lastname: Ren
mesh_terms: D002478:Cells, Cultured; D002788:Cholesterol Esters / Q000378:metabolism*; D002851:Chromatography, High Pressure Liquid; D042783:Endothelial Cells / Q000187:drug effects / Q000201:enzymology*; D005230:Fatty Acids, Nonesterified / Q000378:metabolism; D005786:Gene Expression Regulation; D006801:Humans; D006845:Hydrocarbons, Fluorinated / Q000494:pharmacology; D006888:Hydroxycholesterols / Q000378:metabolism*; D000071518:Liver X Receptors; D057093:Orphan Nuclear Receptors / Q000819:agonists / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D051780:Sterol Regulatory Element Binding Protein 1 / Q000235:genetics / Q000378:metabolism*; D013449:Sulfonamides / Q000494:pharmacology; D015238:Sulfotransferases / Q000235:genetics / Q000378:metabolism*; D013997:Time Factors; D014162:Transfection; D014280:Triglycerides / Q000378:metabolism; D005466:Fluorocarbons; D000096926:Benzenesulfonamides
chemical_list: D002788:Cholesterol Esters; D005230:Fatty Acids, Nonesterified; D006845:Hydrocarbons, Fluorinated; D006888:Hydroxycholesterols; D000071518:Liver X Receptors; D057093:Orphan Nuclear Receptors; D012333:RNA, Messenger; D051780:Sterol Regulatory Element Binding Protein 1; D013449:Sulfonamides; D015238:Sulfotransferases; D014280:Triglycerides; C534977:25-hydroxycholesterol 3-sulfate; C497387:SREBF1 protein, human; C423915:T0901317; D005466:Fluorocarbons; D000096926:Benzenesulfonamides; C007997:25-hydroxycholesterol; C433248:SULT2B1 protein, human