Regulation of metallothionein gene expression by 1 alpha,25-dihydroxyvitamin D3 in cultured cells and in mice.

作者：Masamitu Karasawa, Junichi Hosoi, Haruka Hashiba, Kiyoshi Nose, Chiharu Tohyama, Eiji Abe, Takeshi Suda, Toshio Kuroki · 发表于：Proceedings of the National Academy of Sciences · 年份：1987 · DOI：10.1073/pnas.84.24.8810 · 被引用次数：79 · 研究领域：Trace Elements in Health、Vitamin D Research Studies、Iron Metabolism and Disorders

1 alpha,25-Dihydroxyvitamin D3 [1 alpha,25(OH)2D3], a hormonally active form of vitamin D3, has been shown to modulate cell differentiation and tumor promotion. This report demonstrates that mRNA of the metallothionein (MT) gene was induced by 1 alpha,25(OH)2D3 in cultured epidermal keratinocytes and also in liver, kidney, and skin tissues when 1 alpha-hydroxyvitamin D3, a synthetic precursor of 1 alpha,25(OH)2D3, was applied in vivo. Exposure of FRSK cells, a cell line derived from fetal rat skin keratinocytes, to 1 alpha,25(OH)2D3 at 5 ng/ml (12 nM) increased MT mRNA to almost the same extent as that induced by 10 microM dexamethasone or 1 microM CdCl2. This increase in the level of MT mRNA was evident within 2 hr and was maximal 12-24 hr after the addition of 1 alpha,25(OH)2D3. The induction was dose-dependent with concentrations of 1 alpha,25(OH)2D3 from 0.05 to 5.0 ng/ml. Amounts of MT increased with the increase of MT mRNA induced by 1 alpha,25(OH)2D3. Of the derivatives of vitamin D3 tested, only 1 alpha,25(OH)2D3 caused marked induction. Treatment with cycloheximide did not inhibit MT mRNA induction by 1 alpha,25(OH)2D3. 1 alpha,25(OH)2D3 induced MT mRNA in primary cultures of mouse epidermal keratinocytes but not in IAR-20, a liver cell line. 1 alpha,25(OH)2D3 had a similar effect in vivo: oral administration of 1 alpha-hydroxyvitamin D3 to mice resulted in increased levels of MT mRNA in the liver, kidney, and skin 24 hr later. Increase in the level of MT mRNA may be...