Characterization of vitamin D-mediated induction of the CYP 24 transcription.
Transcription of the CYP24 (25-hydroxyvitamin D(3)-24-hydroxylase) gene is known to be induced by 1alpha,25-dihydroxyvitamin D3 (1,25(OH)2D3). We studied the induction kinetics in detail in human skin-derived fibroblasts. While the basal transcription of this gene was very low, addition of 1,25(OH)2D3 increased the mRNA level by 50-fold within 1h. The induction reached as high as 20000-fold after 12h. DNA microarray analysis also indicated that the induction ratio of the CYP24 gene is exceptionally high among 3800 human genes examined. The increase of mRNA was caused by stimulation of the transcription, but not by stabilization of mRNA. 24(R),25-dihydroxyvitamin D3 (24,25(OH)2D3), a compound metabolically related to 1,25(OH)2D3, also stimulated the CYP24 gene transcription, though at much higher concentrations. However, this stimulation was significantly augmented by synergistic actions of 24,25(OH)2D3 and 1,25(OH)2D3, suggesting that 24,25(OH)2D3 or its metabolites might be playing some roles in the regulation of CYP24 gene transcription.
Laboratory of Molecular Biology, Department of Bioresources, Hiroshima Prefectural University, 562 Nanatsuka, Shobara, Hiroshima 727-0023, Japan.
Katsuhisa
K
Tashiro
Takaya
T
Abe
Naohide
N
Oue
Wataru
W
Yasui
Masaru
M
Ryoji
D015650:24,25-Dihydroxyvitamin D 3 / Q000494:pharmacology; D002117:Calcitriol / Q000494:pharmacology; D002120:Calcium Channel Agonists / Q000494:pharmacology; D002478:Cells, Cultured; D003577:Cytochrome P-450 Enzyme System / Q000235:genetics* / Q000378:metabolism; D004357:Drug Synergism; D004789:Enzyme Activation / Q000187:drug effects; D005347:Fibroblasts / Q000201:enzymology*; D020869:Gene Expression Profiling; D006801:Humans; D020411:Oligonucleotide Array Sequence Analysis; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D012867:Skin / Q000201:enzymology*; D013250:Steroid Hydroxylases / Q000235:genetics* / Q000378:metabolism; D014158:Transcription, Genetic / Q000187:drug effects*; D014807:Vitamin D / Q000378:metabolism*; D065668:Vitamin D3 24-Hydroxylase
D002120:Calcium Channel Agonists; D012333:RNA, Messenger; D014807:Vitamin D; D015650:24,25-Dihydroxyvitamin D 3; D003577:Cytochrome P-450 Enzyme System; D013250:Steroid Hydroxylases; D065668:Vitamin D3 24-Hydroxylase; D002117:Calcitriol