Identification and Characterization of the Human Cytosolic Sulfotransferases Mediating the Sulfation of Clioquinol and Iodoquinol

Title:Identification and Characterization of the Human Cytosolic Sulfotransferases Mediating the Sulfation of Clioquinol and Iodoquinol

Volume: 10 Issue: 3

Author(s): Akihiro Yamamoto, Maame Debrah-Pinamang, Nicholas J. DiModica, Katsuhisa Kurogi, Ali A. Naqvi, Ying Hui, Yoichi Sakakibara, Masahito Suiko and Ming-Cheh Liu

Affiliation:

Keywords: Clioquinol, cytosolic sulfotransferase, iodoquinol, sulfation, SULT.

Abstract: Objective: 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.

Method: 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.

Results: 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.

Conclusion: Collectively, these results provided a molecular basis underling the metabolism of clioquinol and iodoquinol through sulfation.

Cite this article as:

Yamamoto Akihiro, Debrah-Pinamang Maame, DiModica J. Nicholas, Kurogi Katsuhisa, Naqvi A. Ali, Hui Ying, Sakakibara Yoichi, Suiko Masahito and Liu Ming-Cheh, Identification and Characterization of the Human Cytosolic Sulfotransferases Mediating the Sulfation of Clioquinol and Iodoquinol, Drug Metabolism Letters 2016; 10 (3) . https://dx.doi.org/10.2174/1872312810666160719142850