High ER stress in β-cells stimulates intracellular degradation of misfolded insulin
High ER stress in β-cells stimulates intracellular degradation of misfolded insulin
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DOI：
10.1016/j.bbrc.2004.09.035
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发表时间：
2004-11-05
影响因子：
3.1
通讯作者：
Urano, F
中科院分区：
文献类型：
--
作者：
Allen, JR;Nguyen, LX;Urano, F
内质网应激是由错误折叠的蛋白质在内质网中堆积引起的，它会引起一种适应性反应，即未折叠蛋白反应(UPR)。内质网相关蛋白降解系统(ERAD)是UPR的一个组成部分，在内质网应激细胞的生存中起着重要的作用。在这里，我们展示了ERAD系统的一个组成部分Hrd1在秋田糖尿病小鼠模型的胰岛中上调，并增强了错误折叠的胰岛素的细胞内降解。β细胞中的高内质网应激通过Hrd1刺激突变的胰岛素降解，以保护贝塔细胞免受内质网应激和随后的死亡。如果Hrd1在人类身上具有相同的功能，它可能会成为糖尿病治疗干预的靶点。(C)2004 Elsevier Inc.保留所有权利。
Endoplasmic reticulm (ER) stress, which is caused by the accumulation of misfolded proteins in the ER, elicits an adaptive response, the unfolded protein response (UPR). One component of the UPR, the endoplasmic reticulum-associated protein degradation (ERAD) system, has an important function in the survival of ER stressed cells. Here, we show that HRD1, a component of the ERAD system, is upregulated in pancreatic islets of the Akita diabetes mouse model and enhances intracellular degradation of misfolded insulin. High ER stress in beta-cells stimulated mutant insulin degradation through HRD1 to protect beta-cells from ER stress and ensuing death. If HRD1 serves the same function in humans, it may serve as a target for therapeutic intervention in diabetes. (C) 2004 Elsevier Inc. All rights reserved.