Relationship between the induction of heat shock proteins and the decrease in glucocorticoid receptor during heat shock response in human osteosarcoma cells.

Abstract

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 hsp90 alpha 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 in GR 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.