1α,24(S)-dihydroxyvitamin D2: a biologically active product of 1α-hydroxyvitamin D2 made in the human hepatoma, Hep3B
| Autor: | J C Knutson, R M Moriarty, C W Bishop, L W LeVan, Stephen Strugnell, R Gilardi, Glenville Jones, Valarie Byford, Hugh L.J. Makin |
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| Rok vydání: | 1995 |
| Předmět: |
Chloramphenicol O-Acetyltransferase
Vitamin Carcinoma Hepatocellular Metabolite Alpha (ethology) Biology Biochemistry Calcitriol receptor Gas Chromatography-Mass Spectrometry Cell Line Chloramphenicol acetyltransferase chemistry.chemical_compound Genes Reporter Chlorocebus aethiops Tumor Cells Cultured Animals Humans Molecular Biology Reporter gene Liver cell Stereoisomerism Biological activity Cell Biology Rats chemistry Ergocalciferols Receptors Calcitriol Cattle Research Article |
| Zdroj: | Biochemical Journal. 310:233-241 |
| ISSN: | 1470-8728 0264-6021 |
| DOI: | 10.1042/bj3100233 |
| Popis: | A major metabolite of the vitamin D analogue 1 alpha-hydroxyvitamin D2 in human liver cells in culture has been identified as 1 alpha,24(S)-dihydroxyvitamin D2 [1 alpha,24(S)-(OH)2D2]. 1 alpha-Hydroxyvitamin D3 incubated with the same cells gives rise to predominantly 25- and 27-hydroxylated products. Our identification of 1 alpha,24(S)-dihydroxyvitamin D2 is based on comparisons of the liver cell metabolite with chemically synthesized 1 alpha,24(S)-(OH)2D2 and 1 alpha,24(R)-(OH)2D2 by using HPLC, GC and GC-MS techniques. The stereochemical orientation of the 24-hydroxyl group was inferred after X-ray-crystallographic analysis of the 24(R)-OH epimer. 1 alpha,24(S)-Dihydroxyvitamin D2 binds strongly to the vitamin D receptor and is biologically active in growth hormone and chloramphenicol acetyltransferase reporter gene expression systems in vitro, but binds poorly to rat vitamin D-binding globulin, DBP. We suggest that this metabolite, 1 alpha,24(S)-(OH)2D2, possesses the spectrum of biological properties to be useful as a drug in the treatment of psoriasis, metabolic bone disease and cancer. |
| Databáze: | OpenAIRE |
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