title: Identification and Characterization of the Human Cytosolic Sulfotransferases Mediating the Sulfation of Clioquinol and Iodoquinol.
abstract: The aim of the current study was to identify the human cytosolic sulfotransferases (SULTs) that are capable of sulfating clioquinol and iodoquinol, and to verify the presence of clioquinol/ iodoquinol-sulfating activity in human organ homogenates and cultured cells.
  
  
  
  An established sulfotransferase assay was employed to analyze clioquinol/iodoquinolsulfating activity of thirteen known human SULTs, as well as cytosols of human kidney, liver, lung, and small intestine. Metabolic labeling with [35S]sulfate in the presence of different concentrations of clioquinol/iodoquinol was performed using cultured HepG2 human hepatoma cells and Caco-2 human colon carcinoma cells.
  
  
  
  A systematic analysis revealed that six of the thirteen known human SULTs, SULT1A1 SULT1A2, SULTA3, SULT1B1, SULT1C4, and SULT1E1 showed considerable clioquinol/ iodoquinol-sulfating activity. Kinetic parameters of the sulfation of clioquinol and iodoquinol by three SULTs, SULT1A1, SULT1A3, and SULT1C4, that showed the strongest clioquinol/iodoquinolsulfating activity were determined. Moreover, clioquinol/iodoquinol-sulfating activity was detected in the cytosol fractions of human liver, lung, kidney, and small intestine. Cultured HepG2 and Caco-2 cells were shown to be capable of sulfating clioquinol/iodoquinol under metabolic conditions.
  
  
  
  Collectively, these results provided a molecular basis underling the metabolism of clioquinol and iodoquinol through sulfation.
authors.forename: Akihiro
authors.initials: A
authors.lastname: Yamamoto
authors.forename: Maame
authors.initials: M
authors.lastname: Debrah-Pinamang
authors.forename: Nicholas J
authors.initials: NJ
authors.lastname: DiModica
authors.forename: Katsuhisa
authors.initials: K
authors.lastname: Kurogi
authors.forename: Ali A
authors.initials: AA
authors.lastname: Naqvi
authors.forename: Ying
authors.initials: Y
authors.lastname: Hui
authors.forename: Yoichi
authors.initials: Y
authors.lastname: Sakakibara
authors.forename: Masahito
authors.initials: M
authors.lastname: Suiko
authors.affiliation: Department of Pharmacology, College of Pharmacy and Pharmaceutical Sciences, University of Toledo Health Science Campus, 3000 Arlington Avenue, Toledo, OH 43614 USA.
authors.forename: Ming-Cheh
authors.initials: MC
authors.lastname: Liu
mesh_terms: D000563:Amebicides / Q000008:administration & dosage / Q000378:metabolism; D018938:Caco-2 Cells; D007464:Clioquinol / Q000008:administration & dosage / Q000378:metabolism*; D003600:Cytosol / Q000201:enzymology / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D056945:Hep G2 Cells; D006801:Humans; D004103:Iodoquinol / Q000008:administration & dosage / Q000378:metabolism*; D013431:Sulfates / Q000378:metabolism; D015238:Sulfotransferases / Q000378:metabolism*
chemical_list: D000563:Amebicides; D013431:Sulfates; D004103:Iodoquinol; D007464:Clioquinol; D015238:Sulfotransferases