Abstract

The role of two heat shock proteins, Hsp70 and Hsp90α, on stress response in mice with severe diabetes mellitus induced by a high dose of alloxan (500 mg/kg body weight), as well as in RIN-m5F β cells cultured in the presence of cytokines (IL-1 and TNF-α) was studied. Our results showed that severe type 1 diabetes mellitus (T1D) caused a higher expression of Hsp90α, but not Hsp70. Moreover, injections of the peroxiredoxin 6 antioxidant enzyme (PRDX6) did not affect the expression of these chaperones. Conversely, pro-inflammatory cytokines added to β-cells caused a significant increase in the expression of Hsp90α and, substantially, Hsp70. Moreover, cells cultivated in the presence of PRDX6 were more susceptible to the cytokine effect. Thus, in the course of severe alloxan-induced T1D, no protective role of the heat shock proteins, was revealed, and their expression level was not increased by PRDX6. At the same time the protective potential of these proteins was shown in vitro with the use of RIN-m5F β cells. Thus, the system of heat shock proteins was unable to prevent the devastating effects of severe T1D accompanied by high animal mortality.

中文翻译：

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Hsp70和Hsp90α热休克蛋白在1型糖尿病过程中参与应激反应。

摘要

两种热休克蛋白Hsp70和Hsp90α在高剂量四氧嘧啶（500 mg / kg体重）诱导的重症糖尿病小鼠以及在存在条件下培养的RIN-m5Fβ细胞中对应激反应的作用研究了细胞因子（IL-1和TNF-α）的表达。我们的结果表明，严重的1型糖尿病（T1D）引起Hsp90α的较高表达，但不引起Hsp70的较高表达。此外，注射过氧化物酶6抗氧化剂（PRDX6）不会影响这些伴侣的表达。相反，添加到β细胞的促炎细胞因子导致Hsp90α以及实质上Hsp70的表达显着增加。而且，在PRDX6存在下培养的细胞更容易受到细胞因子作用的影响。因此，在严重的四氧嘧啶诱导的T1D过程中，没有发现热激蛋白的保护作用，PRDX6并没有增加它们的表达水平。同时，使用RIN-m5Fβ细胞在体外显示了这些蛋白质的保护潜力。因此，热休克蛋白系统无法防止伴随着高动物死亡率的严重T1D的毁灭性影响。