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首页> 外文期刊>Physiological Reviews >Endoplasmic reticulum stress signaling in disease.
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Endoplasmic reticulum stress signaling in disease.

机译：内质网应激信号在疾病中。

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摘要

The extracellular space is an environment hostile to unmodified polypeptides. For this reason, many eukaryotic proteins destined for exposure to this environment through secretion or display at the cell surface require maturation steps within a specialized organelle, the endoplasmic reticulum (ER). A complex homeostatic mechanism, known as the unfolded protein response (UPR), has evolved to link the load of newly synthesized proteins with the capacity of the ER to mature them. It has become apparent that dysfunction of the UPR plays an important role in some human diseases, especially those involving tissues dedicated to extracellular protein synthesis. Diabetes mellitus is an example of such a disease, since the demands for constantly varying levels of insulin synthesis make pancreatic beta-cells dependent on efficient UPR signaling. Furthermore, recent discoveries in this field indicate that the importance of the UPR in diabetes is not restricted to the beta-cell but is also involved in peripheral insulin resistance. This review addresses aspects of the UPR currently understood to be involved in human disease, including their role in diabetes mellitus, atherosclerosis, and neoplasia.
机译：细胞外空间是对未修饰的多肽不利的环境。因此，许多通过分泌或在细胞表面展示而暴露于这种环境的真核蛋白需要在专门的细胞器内质网（ER）中成熟。已经发展出一种复杂的稳态机制，称为未折叠的蛋白质反应（UPR），将新合成蛋白质的负载与ER使它们成熟的能力联系起来。显然，UPR的功能障碍在某些人类疾病中起着重要作用，特别是涉及专门用于细胞外蛋白质合成的组织的疾病。糖尿病是这种疾病的一个例子，因为对胰岛素合成水平不断变化的需求使得胰腺β细胞依赖于有效的UPR信号传导。此外，该领域的最新发现表明，UPR在糖尿病中的重要性不仅限于β细胞，而且还涉及外周胰岛素抵抗。这篇综述针对目前被认为与人类疾病有关的普遍定期审议的各个方面，包括其在糖尿病，动脉粥样硬化和瘤形成中的作用。

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