A reappraisal of the 6-O-desmethylnaproxen-sulfating activity of the human cytosolic sulfotransferases
| Autor: | Fatemah A. Alherz, Noor Hussein, Ming-Cheh Liu Liu, Daniyah A. Almarghalani, Katsuhisa Kurogi |
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| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
Naproxen Physiology Ph optimum Metabolite 030226 pharmacology & pharmacy 03 medical and health sciences chemistry.chemical_compound Cytosol 0302 clinical medicine Sulfation Colon carcinoma Desmethylnaproxen Physiology (medical) medicine Humans Enzyme Assays Pharmacology Sulfates Chemistry Hep G2 Cells General Medicine Orders of magnitude (mass) Kinetics 030104 developmental biology Biochemistry Caco-2 Cells Sulfotransferases human activities medicine.drug |
| Zdroj: | Canadian Journal of Physiology and Pharmacology. 95:647-651 |
| ISSN: | 1205-7541 0008-4212 |
| DOI: | 10.1139/cjpp-2016-0403 |
| Popis: | In this study, we aimed to obtain a comprehensive account of the human cytosolic sulfotransferases (SULTs) that are capable of sulfating 6-O-desmethylnaproxen (O-DMN), a major metabolite of naproxen. Of the 13 known human SULTs tested, 7 (SULT1A1, SULT1A2, SULT1A3, SULT1B1, SULT1C2, SULT1C4, and SULT1E1) displayed O-DMN-sulfating activity, when analyzed using an elevated substrate concentration (500 μmol·L−1) together with 14 μmol·L−1 of the sulfate donor, 3′-phosphoadenosine-5′-phosphosulfate (PAPS). At 10 μmol·L−1 O-DMN concentration, however, only SULT1A1 and SULT1A3 displayed detectable activity, with the former being nearly 2 orders of magnitude more active than the latter. A pH-dependence study indicated that SULT1A1 exhibited a broad pH optimum spanning pH 5.5–7. Kinetic parameters of the sulfation of O-DMN by SULT1A1 were determined. The production and release of sulfated O-DMN was demonstrated using cultured human HepG2 hepatoma cells and Caco-2 colon carcinoma cells. Moreover, assays using human organ specimens revealed that the O-DMN-sulfating activities present in the cytosols of liver and small intestine (at 502.5 and 497.2 pmol·min−1·(mg protein)−1, respectively) were much higher than those detected for the cytosols of lung and kidney. Taken together, these results provided relevant information concerning the sulfation of O-DMN both in vitro and in vivo. |
| Databáze: | OpenAIRE |
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