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以人骨肉瘤细胞系HOS-8603为细胞模型进一步研究了热休克反应过程中热休克蛋白诱导和糖皮质激素受体(GR)结合活性减少之间的相互关系.结果表明,槲皮素虽能抑制热休克蛋白(hsp70和hsp90α)mRNA的表达,并能阻止热耐受功能的建立,但却不能阻止热休克引起的GR结合活性的快速减少,证明在热休克反应过程中热休克蛋白诱导和GR减少是两个相对独立发生的生物学过程.结果还表明,热休克本身虽然对HOS-8603细胞碱性磷酸酶(AKP)活性无明显影响,但可完全抑制糖皮质激素对该酶活性的诱导作用,证明热休克引起的GR减少同时伴有受体功能活性的降低.而且,即使首先用槲皮素预处理,抑制热休克蛋白的诱导,仍然能够完全抑制糖皮质激素对AKP活性的诱导,从功能上进一步证明,槲皮素虽然可以抑制热休克蛋白的诱导,但却不能阻止GR的减少.文中还证明槲皮素对GR具有降调作用且具有明显的时间依赖性特点;槲皮素降调GR的同时伴有糖皮质激素效应的降低.
To further investigate the correlation between heat shock response and reduced glucocorticoid receptor (GR) binding activity in human osteosarcoma cell line HOS-8603, the results showed that although quercetin inhibited The expression of heat shock proteins (hsp70 and hsp90α) mRNA, and can prevent the establishment of heat tolerance function, but can not prevent the rapid reduction of heat shock induced GR binding activity, proving that heat shock protein induced heat shock protein and GR Reduction is a biological process that occurs relatively independently.The results also show that although heat shock itself has no significant effect on alkaline phosphatase (AKP) activity of HOS-8603 cells, glucocorticoid can completely inhibit the induction of the enzyme activity Role in proving the decrease of GR induced by heat shock accompanied with the decrease of functional activity of receptor.Moreover, pretreatment with quercetin and inhibition of heat shock protein can still completely inhibit the induction of AKP activity by glucocorticoid, It is further proved that quercetin can inhibit the induction of heat shock protein, but it can not prevent the reduction of GR. Quercetin has also been shown to have a down-regulation of GR There is a clear time-dependent characteristics; quercetin down-regulation of GR accompanied by a decrease in glucocorticoid effect.