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首页> 外文期刊>Science in China, series B. Chemistry,Life Sciences and Earth Sciences >Relationship between the induction of heat shock proteins and the decrease in glucocorticoid receptor during heat shock response in human osteosarcoma cells
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Relationship between the induction of heat shock proteins and the decrease in glucocorticoid receptor during heat shock response in human osteosarcoma cells

机译：人骨肉瘤细胞热激反应过程中热激蛋白诱导与糖皮质激素受体减少的关系

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摘要

Previously, it has been found that glucocorticoid receptor (GR) binding activity decreased rapidly during heat shock response in HOS-8603, a human osteosarcoma cell line. In this study, The relationship between the induction of heat shock proteins (HSPs) and the decrease in GR was further studied in the same cell line. It was found that even though quercetin could specifically inhibit the expression of hsp90a and hsp70 mRNA, it could not prevent GR from the decrease in response to the heat shock treatment. This represents the first reported evidence that the induction of HSPs and the decrease in GR during heat shock response were 2 independent biological events. The results of the present study further showed that although the heat shock treatment alone had no effects on alkaline phosphatase (AKP) activity, it could completely block the induction of AKP activity in HOS-8603 cells by dexamethasone (Dex), a synthetic glucocorticoid. These results demonstrate that the heat shock-induced alteration inGR was accompanied by a decrease in GR functional activity Furthermore, when the induction of HSPs was inhibited by the treatment of cells with quercetin, the stimulatory effects of Dex on AKP activity could still be inhibited completely by the heat shock treatment. The results of this part, on the basis of GR functional activity, further demonstrate that quercetin could not inhibit the heat shock-induced decrease in GR even though it could inhibit the induction of HSPs. To clarify further the effects of quercetin alone on GR binding activity in HOS-8603 cells, the regulation of GR by quercetin was also studied. It was found for the first time that quercetin could down-regulate GR in a time-dependent manner significantly, and that the down-regulation of GR by quercetin in HOS-8603 cells paralelled with a decrease in glucocorticoid-mediated functional responses, suggesting that the down-regulation of GR by quercetin is of biological significance.
机译：以前，已经发现在人骨肉瘤细胞系HOS-8603的热激反应过程中，糖皮质激素受体（GR）的结合活性迅速降低。在这项研究中，在同一细胞系中进一步研究了热激蛋白（HSPs）的诱导与GR降低之间的关系。已经发现，尽管槲皮素可以特异性抑制hsp90a和hsp70 mRNA的表达，但是它不能阻止GR响应于热激处理而降低。这代表了第一个报道的证据，即热休克反应中HSP的诱导和GR的降低是2个独立的生物学事件。本研究的结果进一步表明，尽管单独进行热休克处理对碱性磷酸酶（AKP）活性没有影响，但它可以完全阻止合成糖皮质激素地塞米松（Dex）对HOS-8603细胞中AKP活性的诱导。这些结果表明，热激诱导的GR改变伴随着GR功能活性的降低。此外，当槲皮素处理细胞抑制HSPs的诱导时，Dex对AKP活性的刺激作用仍可被完全抑制。通过热冲击处理。根据GR功能活性，该部分的结果进一步表明，槲皮素即使可以抑制HSP的诱导，也不能抑制热激诱导的GR的降低。为了进一步阐明槲皮素对HOS-8603细胞中GR结合活性的影响，还研究了槲皮素对GR的调节作用。首次发现槲皮素可以显着地以时间依赖性方式下调GR，而槲皮素在HOS-8603细胞中对GR的下调与糖皮质激素介导的功能性反应减少有关。槲皮素对GR的下调具有生物学意义。

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