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首页> 外文期刊>Cellular Physiology and Biochemistry >Genetic variations of heat shock protein 84 in mice mediate cellular glucocorticoid response
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Genetic variations of heat shock protein 84 in mice mediate cellular glucocorticoid response

机译：小鼠热休克蛋白84的遗传变异介导细胞糖皮质激素反应

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摘要

Heat shock protein 90 (Hsp90), encoded by hsp84 and hsp86 in mice, has been confirmed to modulate glucocorticoid receptor (GR) function; however, the contribution of Hsp90 in glucocorticoid (GC) sensibility/resistance has received less attention. Previously, we found that genetic variations of Hsp84 are related to differences in the in vivo GC-GR responses between BALB/c and C57BL/6 mice suffering from traumatic injury. To evaluate the modulation of Hsp84 polymorphisms on the GC response, we used a cellular heat-stress injury (HSI) model combined with a transgene-plasmid infection approach and assessed HSI-induced cellular damage and GR nuclear translocation, with or without dexamethasone pretreatment. We demonstrated that after HSI, fibroblasts from the C57BL/6 line exhibit higher cellular survival, higher nuclear GR levels and lower lactate dehydrogenase activity compared to those from the BALB/c line. We showed that dexamethasone-rescued HSI-induced damage is accompanied by increasing nuclear GR levels in both lines. Importantly, this protection against HSI was greater in C57BL/6 fibroblasts and was resistant to geldanamycin, a selective inhibitor of Hsp90. Importantly, transfection of the hsp84-transgene from C57BL/6 mice increased the nuclear GR levels and lessened HSI-induced damage in BALB/c fibroblasts. Our data thereby demonstrate that Hsp84 from C57BL/6 mice modulates higher cellular GC-GR responsiveness.
机译：已经证实在小鼠中由hsp84和hsp86编码的热休克蛋白90（Hsp90）可以调节糖皮质激素受体（GR）的功能。但是，Hsp90在糖皮质激素（GC）敏感性/抗性中的贡献受到的关注较少。以前，我们发现Hsp84的遗传变异与遭受创伤性损伤的BALB / c和C57BL / 6小鼠体内GC-GR反应的差异有关。为了评估Hsp84基因多态性对GC反应的调节作用，我们使用了细胞热应激损伤（HSI）模型与转基因质粒感染方法相结合，并评估了HSI诱导的细胞损伤和GR核易位，有或没有地塞米松预处理。我们证明了在HSI之后，与来自BALB / c系的相比，来自C57BL / 6系的成纤维细胞显示出更高的细胞存活率，更高的核GR水平和更低的乳酸脱氢酶活性。我们显示，地塞米松挽救的HSI诱导的损害伴随着两条系中核GR含量的增加。重要的是，这种对HSI的保护作用在C57BL / 6成纤维细胞中更大，并且对格尔德霉素（一种Hsp90的选择性抑制剂）具有抵抗力。重要的是，转染来自C57BL / 6小鼠的hsp84-转基因可提高BALB / c成纤维细胞的核GR水平，并减少HSI诱导的损伤。因此，我们的数据证明，来自C57BL / 6小鼠的Hsp84调节更高的细胞GC-GR反应性。

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