Wang Jing-Huan, Tuohimaa Pentti
Department of Anatomy, Medical School, 33014 University of Tampere, Tampere, Finland.
Biochem Biophys Res Commun. 2006 Jun 30;345(2):720-5. doi: 10.1016/j.bbrc.2006.04.156. Epub 2006 May 5.
Vitamin D3 plays an important role in the control of cell proliferation and differentiation. Cholesterol 25-hydroxylase (CH25H) is an enzyme converting cholesterol into 25-hydroxycholesterol. Vitamin D3 as well as 25-hydroxycholesterol has been shown to inhibit cell growth and induce cell apoptosis. Here we show that 10 nM 1alpha,25(OH)2D3 and 500 nM 25OHD3 upregulate CH25H mRNA expression in human primary prostate stromal cells (P29SN). Protein synthesis inhibitor cycloheximide does not block 1alpha,25(OH)2D3 mediated upregulation of CH25H mRNA. Transcription inhibitor actinomycin D blocks basal level as well as 1alpha,25(OH)2D3 induced CH25H mRNA expression. 1alpha,25(OH)2D3 has no effect on CH25H mRNA stability. 25-Hydroxycholesterol significantly decreased the P29SN cell number. A CH25H enzyme inhibitor, desmosterol, increases basal cell number but has no significant effect on vitamin D3 treated cells. Our data suggest that ch25h could be a vitamin D3 target gene and may partly mediate anti-proliferative action of vitamin D3 in human primary prostate stromal cells.
维生素D3在细胞增殖和分化的调控中发挥着重要作用。胆固醇25-羟化酶（CH25H）是一种将胆固醇转化为25-羟胆固醇的酶。维生素D3以及25-羟胆固醇已被证明可抑制细胞生长并诱导细胞凋亡。在此我们表明，10 nM的1α,25(OH)2D3和500 nM的25OHD3可上调人原代前列腺基质细胞（P29SN）中CH25H mRNA的表达。蛋白质合成抑制剂放线菌酮不会阻断1α,25(OH)2D3介导的CH25H mRNA上调。转录抑制剂放线菌素D可阻断基础水平以及1α,25(OH)2D3诱导的CH25H mRNA表达。1α,25(OH)2D3对CH25H mRNA稳定性没有影响。25-羟胆固醇显著降低了P29SN细胞数量。一种CH25H酶抑制剂，去氢胆固醇，增加了基础细胞数量，但对维生素D3处理的细胞没有显著影响。我们的数据表明，CH25H可能是维生素D3的靶基因，并且可能部分介导维生素D3在人原代前列腺基质细胞中的抗增殖作用。
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