Metabolism of 26,27-hexafluoro-1 alpha,25-dihydroxyvitamin D3 and 26,27-hexafluoro-1 alpha,23(S)25-trihydroxyvitamin D3 in ROS17/2.8 cells transfected with a plasmid expressing CYP24 |
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Authors: | Miyahara T Gomyo S Ueda Y Ohyama Y Sigeno C Kozakai A Takamura T Yamazaki R Higuchi S Yamamoto M Sakuma T Nemoto N |
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Institution: | Department of Toxicology, Faculty of Pharmaceutical Sciences, Toyama Medical & Pharmaceutical University, 2630 Sugitani, Toyama-shi, Toyama, 930-0194, Japan. |
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Abstract: | 1. To clarify the possibility that the metabolism of 26,27-hexafluoro-1 alpha,25-dihydroxyvitamin D3 F6-1,25(OH)2D3] to 26,27-hexafluoro-1 alpha,23(S),25-trihydroxyvitamin D3 F6-1,23,25(OH)3D3 and that of F6-1,23,25(OH)3D3 to 26,27-hexafluoro-23-oxo-1 alpha,25-dihydroxyvitamin D3 F6-23-oxo-1,25(OH)2D3] are catalysed by 25-hydroxyvitamin D3 24-hydroxylase (CYP24), ROS17/2.8 cells transfected with a plasmid expressing CYP24 pSVL-CYP24(+)] and a corresponding blank plasmid pSLV-CYP24R(-)] were used. 2. Incubation of 1 beta-3H]-F6-1,25(OH)2D3 for 2 and 5 days with ROS17/2.8 cells transfected with pSVL-CYP24(+) generated a metabolite that co-migrated with authentic F6-1,23,25(OH)3D3 in both normal phase and reversed-phase HPLC systems. 3. Incubation of 1 beta-3H]-F6-1,23,25(OH)3D3 for 5 days with pSVL-CYP24(+)- transfected ROS 17/2.8 cells generated a metabolite that co-migrated with authentic F6-23-oxo-1,25(OH)2D3. In contrast, the metabolites F6-1,23,25(OH)3D3 or F6-23-oxo-1,25(OH)2D3 were not generated in the cells transfected with pSVL-CYP24R(-). 4. The results indicate that CYP24 catalyses the conversion of F6-1,25(OH)2D3 to F6-1,23,25(OH)3D3 and that of F6-1,23,25(OH)3D3 to F6-23-oxo-1,25(OH)2D3. |
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