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Updated: Jul 25, 2026
Biochemical Reconstitution of Steroid Receptor•Hsp90 Protein Complexes and Reactivation of Ligand Binding
Published on: September 21, 2011
Relationship between the induction of heat shock proteins and the decrease in glucocorticoid receptor during heat
1Department of Pathophysiology, Second Military Medical University, Shanghai, China.
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.
Insights
Heat shock response independently decreases glucocorticoid receptor (GR) activity and induces heat shock proteins (HSPs). Quercetin inhibits HSPs but not GR decrease, showing these are separate events. GR down-regulation by quercetin also impairs cell response.
Area of Science:
- Cell Biology
- Molecular Biology
- Biochemistry
Background:
- Glucocorticoid receptor (GR) binding activity decreases during heat shock in HOS-8603 cells.
- Heat shock proteins (HSPs) are induced during heat shock response.
Purpose of the Study:
- To investigate the relationship between heat shock protein induction and GR decrease during heat shock response.
- To determine if quercetin affects GR activity and HSP induction.
- To examine the impact of heat shock on GR functional activity and dexamethasone-induced responses.
Main Methods:
- Utilized HOS-8603 human osteosarcoma cell line.
- Administered heat shock treatment.
- Applied quercetin to inhibit HSP expression.
- Measured GR binding activity and alkaline phosphatase (AKP) activity.
- Assessed dexamethasone (Dex)-induced AKP activity.
Main Results:
- Quercetin inhibited hsp90 alpha and hsp70 mRNA expression but did not prevent GR decrease during heat shock.
- Heat shock alone did not affect AKP activity but blocked dexamethasone-induced AKP activity, indicating decreased GR functional activity.
- Quercetin treatment did not prevent heat shock-induced GR decrease, even when HSP induction was inhibited.
- Quercetin significantly down-regulated GR in a time-dependent manner, paralleling decreased glucocorticoid-mediated responses.
Conclusions:
- Heat shock protein induction and GR decrease during heat shock are independent biological events.
- Heat shock-induced GR alteration is associated with reduced GR functional activity.
- Quercetin down-regulates GR, impacting glucocorticoid-mediated cellular functions.
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