标题:Isolation, Identification and Biological Activity of 24R, 25-Dihydroxy-3-epi vitamin D3: A Novel Metabolite of 24R, 25-Dihydroxyvitamin D3 Produced in Rat Osteosarcoma Cells (UMR 106)
期刊名称:Journal of Nutritional Science and Vitaminology
印刷版ISSN:0301-4800
电子版ISSN:1881-7742
出版年度:2001
卷号:47
期号:2
页码:108-115
DOI:10.3177/jnsv.47.108
出版社:Center for Academic Publications Japan
摘要:We recently identified 1α, 25-dihydroxy-3-epi-vitamin D3 [1 α, 25(OH)2-3-epi-D3] as a metabolite of 1 α, 25-dihydroxyvitamin D3 [1α, 25(OH)2D3] produced in rat osteosarcoma cells (UMR 106). We now report the isolation of 24 R , 25-dihydroxy-3-epi-vitamin D3 [24 R , 25 (OH)2-3-epi-D3] as a metabolite of 24 R , 25-dihydroxyvitamin D3 [24 R , 25(OH)2D3] by high-performance liquid chromatography (HPLC) with chiral column and its structure assignment by proton nuclear magnetic resonance (1H-NMR) and liquid chromatography-mass spectrometry (LC-MS) analysis. We also demonstrated the production of 24 R , 25(OH)2-3-epi-D3 in two other cell lines [human colon carcinoma cells (Caco-2) and porcine kidney cells (LLC-PK1)] which were previously shown to convert 1 α, 25(OH)2D3 into 1 α, 25 (OH)2-3-epi-D3. It can be seen that the production of 24 R , 25 (OH)2-3-epi-D3 from 24 R , 25(OH)2D3 is lower than that of 1 α, 25 (OH)2-3-epi-D3 from 1α, 25(OH)2D3 in all the cells studied. 24 R , 25(OH)2-3-epi-D3 was found to be inactive in terms of its ability to bind to the vitamin D receptor (UDR), in inhibiting proliferation and in inducing differentiation of human promyelocytic leukemia cells (HL-60). Thus, our study indicates that the C-3 epimerization pathway is common to both lα, 25(OH)2D3 and 24 R , 25(OH)2D3 and may play an important role in modulating the concentration and the biological activity of these two major vitamin D3 metabolites in target tissues.