THE RAPID NONGENOMIC ACTIONS OF 1-ALPHA,25-DIHYDROXYVITAMIN-D3 MODULATE THE HORMONE-INDUCED INCREMENTS IN OSTEOCALCIN GENE-TRANSCRIPTION IN OSTEOBLAST-LIKE CELLS
THE RAPID NONGENOMIC ACTIONS OF 1-ALPHA,25-DIHYDROXYVITAMIN-D3 MODULATE THE HORMONE-INDUCED INCREMENTS IN OSTEOCALCIN GENE-TRANSCRIPTION IN OSTEOBLAST-LIKE CELLS
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DOI：
10.1002/jcb.240500203
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发表时间：
1992-10-01
影响因子：
4
通讯作者：
LIAN, J
中科院分区：
文献类型：
--
作者：
BARAN, DT;SORENSEN, AM;LIAN, J
我们先前已经证明，1 α，25-二羟维生素D3（1 α，25-（OH）2D 3）的快速非基因组作用之一，细胞内钙（Ca 2+）的增加，伴随着大鼠骨肉瘤细胞中骨钙素（OC）mRNA稳态水平的增加。为了确定非基因组作用的功能意义，我们测量了细胞内Ca 2+的变化作为快速效应的指标，并评估了无活性差向异构体1 β，25-二羟基维生素D3（1 β，25-（OH）2D 3）对OC mRNA稳态水平和转录的抑制作用。1 β，25-二羟维生素D3抑制1 α，25-（OH）2D 3诱导的细胞内Ca ~（2+）和OC mRNA转录在1小时和OC mRNA稳态水平在3小时的增加。1 β，25-二羟维生素D3不改变维生素D受体复合物与OC基因的维生素D反应元件的结合。结果表明，快速，非基因组行动的1 α，25-（OH）2D 3在基因组激活OC基因的激素在大鼠成骨细胞样细胞的功能的重要性，也许通过修改微妙的结构和/或功能特性的维生素D受体DNA复合物或通过影响其他蛋白质DNA相互作用，支持OC基因转录。
We have previously shown that one of the rapid nongenomic actions of 1alpha,25-dihydroxyvitamin D3 (1alpha,25-(OH)2D3), the increase in intracellular calcium (Ca2+), accompanies the increased osteocalcin (OC) mRNA steady-state levels in rat osteosarcoma cells. To determine the functional significance of the nongenomic actions, we have measured changes in intracellular Ca2+ as an indicator of the rapid effects and have assessed the effect of inhibition of the rapid increase in cellular Ca2+ by the inactive epimer, 1beta,25-dihydroxyvitamin D3 (1beta,25-(OH)2D3), on OC mRNA steady-state levels and transcription. 1beta,25-dihydroxyvitamin D3 inhibited 1alpha,25-(OH)2D3 induced increases in intracellular Ca2+ and OC mRNA transcription at 1 hr and OC mRNA steady state levels at 3 hr. 1beta,25-Dihydroxyvitamin D3 did not alter the binding of the vitamin D receptor complex to the vitamin D responsive element of the OC gene. The results demonstrate the functional importance of the rapid, nongenomic actions of 1alpha,25-(OH)2D3 in the genomic activation of the OC gene by the hormone in rat osteoblast-like cells, perhaps by modifying subtle structural and/or functional properties of the vitamin D-receptor DNA complex or by affecting other protein DNA interactions that support OC gene transcription.