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首页> 外文期刊>Journal of psychiatric research >Pattern of heat shock factor and heat shock protein expression inlymphocytes of bipolar patients: Increased HSP70-glucocorticoid receptor heterocomplex
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Pattern of heat shock factor and heat shock protein expression inlymphocytes of bipolar patients: Increased HSP70-glucocorticoid receptor heterocomplex

机译：双相型患者热休克因子和热休克蛋白表达淋巴细胞的模式：HSP70-糖皮质激素受体杂合物增加

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摘要

Bipolar disorder (BD), a stress-related disease, is characterized by altered glucocorticoid receptor (GR) signalling. Stress response includes activation of heat shock factor (HSF) and subsequent heat shock protein (HSP) synthesis which regulate GR folding and function. The objective of this study was to investigate the possible role of HSFs, HSPs and their interaction with GR in BD. We applied immunoprecipitation, SDS-PAGE/Western blot analysis and electrophoretic mobility shift assay (EMSA) in lymphocytes (whole cell or nuclear extracts) from BD patients and healthy subjects and determined the HSPs (HSP90 and HSP70), the heterocomplexes HSP90-GR and HSP70-GR, the HSFs (HSF1 and HSF4) as well as the HSF-DNA binding. The HSP70-GR heterocomplex was elevated (p<0.05) in BD patients vs healthy subjects, and nuclear HSP70 was reduced (p≤0.01) in bipolar manic patients. Protein levels of HSF1, HSF4, HSP90, HSP90-GR heterocomplex, and HSF-DNA binding remained unaltered in BD patients vs healthy subjects. The corresponding effect sizes (ES) indicated a large ES for HSP70-GR, HSP70, HSF-DNA binding and HSF4, and a medium ES for HSP90, HSF1 and HSP90-GR between healthy subjects and bipolar patients. Significant correlations among HSFs, HSPs, GR and HSP70-GR heterocomplex were observed in healthy subjects, which were abrogated in bipolar patients. The higher interaction between GR and HSP70 and the disturbances in the relations among heat shock response parameters and GR as observed in our BD patients may provide novel insights into the contribution of these factors in BD aetiopathogenesis.
机译：躁郁症（BD）是一种与压力有关的疾病，其特征是糖皮质激素受体（GR）信号改变。应激反应包括热休克因子（HSF）的激活和随后的热休克蛋白（HSP）合成，它们调节GR折叠和功能。这项研究的目的是调查HSF，HSP及其与BD中GR相互作用的可能作用。我们对BD患者和健康受试者的淋巴细胞（全细胞或核提取物）进行了免疫沉淀，SDS-PAGE /蛋白质印迹分析和电泳迁移率迁移分析（EMSA），并确定了HSP（HSP90和HSP70），杂合体HSP90-GR和HSP70-GR，HSF（HSF1和HSF4）以及HSF-DNA结合。 BD患者与健康受试者的HSP70-GR异源复合物升高（p <0.05），而双相躁狂患者的核HSP70降低（p≤0.01）。与健康受试者相比，BD患者的HSF1，HSF4，HSP90，HSP90-GR异源复合物和HSF-DNA结合蛋白水平保持不变。相应的效应值（ES）表示健康受试者与双相情感障碍患者之间HSP70-GR，HSP70，HSF-DNA结合和HSF4的ES较大，而HSP90，HSF1和HSP90-GR的ES中等。在健康受试者中观察到HSF，HSPs，GR和HSP70-GR异源复合物之间的显着相关性，而在双相患者中则被取消。在我们的BD患者中观察到，GR与HSP70之间的较高相互作用以及热休克反应参数与GR之间的关系紊乱，可能为这些因素在BD发病机理中的作用提供新的见解。

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