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首页> 外文期刊>Endocrinology >Heat shock protein 27 overexpression mitigates cytokine-induced islet apoptosis and streptozotocin-induced diabetes.
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Heat shock protein 27 overexpression mitigates cytokine-induced islet apoptosis and streptozotocin-induced diabetes.

机译：热休克蛋白27的过表达减轻了细胞因子诱导的胰岛凋亡和链脲佐菌素诱导的糖尿病。

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Beta-cell apoptosis occurs in diabetes mellitus (DM). Heat shock protein (HSP) 27 (human homolog of rodent HSP25) mitigates stress-induced apoptosis but has not been studied in beta-cells. We tested whether HSP27 overexpression attenuates streptozotocin (SZ)-induced DM in vivo and cytokine-induced islet apoptosis in vitro. DM was ascertained by ip glucose tolerance testing, and fasting serum insulin/glucose was measured. Pancreas was stained for insulin, HSP27, and terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick-end labeling, and insulin content was measured. HSP25/27 was measured by immunoblotting, isoelectric focusing, and RT-PCR. Islet HSP25/27 oligomerization and inhibitory kappaB protein kinase gamma (nuclear factor kappaB essential modulator) binding were assessed by coimmunoprecipitation. HSP27 transgene (TG) in pancreas localized predominantly in beta-cells. Baseline pancreatic insulin levels in wild-type (WT) and HSP27TG mice were similar, but lower in WT than HSP27TG after SZ (P < 0.01). Intraperitoneal glucose tolerance testing confirmed protection from SZ-DM in HSP27TG. Terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick-end labeling and inducible nitric oxide synthase staining were increased in WT vs. HSP27TG islets (P < 0.05) after SZ. Caspase-3 activity was lower in islets from HSP27TG vs. WT mice after cytokine stress in vitro (P < 0.05). There was more HSP25 plus 27 protein from HSP27TG islets than HSP25 from WT (P < 0.01). HSP25 protein but not mRNA was increased in HSP27TG mice. Isoelectric focusing showed similar relative HSP phosphorylation in HSP27TG and WT (P > 0.05). HSP27 bound native HSP25 in TG islets; both bound to inhibitory kappaB protein kinase gamma (nuclear factor kappaB essential modulator). These data show islet protection by HSP27 by mitigation of apoptosis, possibly through nuclear factor kappaB regulation.
机译：β细胞凋亡发生在糖尿病（DM）中。热休克蛋白（HSP）27（啮齿动物HSP25的人类同源物）可缓解应激诱导的细胞凋亡，但尚未在β细胞中进行过研究。我们测试了HSP27是否在体内过表达减弱了链脲佐菌素（SZ）诱导的DM和体外细胞因子诱导的胰岛凋亡。通过ip葡萄糖耐量试验确定DM，并测量空腹血清胰岛素/葡萄糖。对胰腺进行胰岛素，HSP27和末端脱氧核苷酸转移酶介导的脱氧尿苷三磷酸缺口末端标记的染色，并测量胰岛素含量。通过免疫印迹，等电聚焦和RT-PCR测量HSP25 / 27。通过共免疫沉淀法评估胰岛HSP25 / 27寡聚和抑制性κB蛋白激酶γ（核因子κB必需调节剂）结合。胰腺中的HSP27转基因（TG）主要位于β细胞中。野生型（WT）和HSP27TG小鼠的基线胰腺胰岛素水平相似，但在SZ后，WT中的基线胰腺胰岛素水平低于HSP27TG（P <0.01）。腹膜内葡萄糖耐量测试证实了HSP27TG对SZ-DM的保护作用。 SZ后，WT与HSP27TG胰岛相比，末端脱氧核苷酸转移酶介导的脱氧尿苷三磷酸缺口末端标记和诱导型一氧化氮合酶染色增加（P <0.05）。体外细胞因子应激后，HSP27TG胰岛中的Caspase-3活性低于WT小鼠（P <0.05）。来自HSP27TG胰岛的HSP25加27种蛋白质比来自WT的HSP25多（P <0.01）。在HSP27TG小鼠中，HSP25蛋白增加了，而mRNA没有增加。等电聚焦显示在HSP27TG和WT中类似的相对HSP磷酸化（P> 0.05）。 HSP27在TG胰岛中结合了天然HSP25两者均与抑制性κ蛋白激酶γ（核因子κB必需调节剂）结合。这些数据表明，通过减轻细胞凋亡（可能通过核因子kappaB调节），HSP27可保护胰岛。

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