Department of Biological Chemistry, Medical School, University of Athens, 75, M. Asias Street, 11527 Athens, Greece.
J Clin Endocrinol Metab. 2012 Jul;97(7):2231-42. doi: 10.1210/jc.2011-3408. Epub 2012 Apr 16.
Advanced glycation, the major posttranslational modification of proteins, DNA, and lipids, is accelerated under conditions of increased oxidative stress, hyperglycemia, and hypoxia contributing to a variety of metabolic diseases such as diabetes mellitus, obesity, inflammation, polycystic ovarian syndrome, ischemic cardiovascular disease, and neurodegenerative disorders. The potential role of advanced glycation in endoplasmic reticulum (ER) homeostasis is largely unknown.
Basic and clinical peer-reviewed articles on advanced glycation and ER stress related to metabolic regulation were searched in PubMed from 2000-2011. The resulting articles as well as relevant cited references were reviewed.
Recent evidence indicates that hyperglycemia, hypoxia, and oxidative stress, apart of triggering advanced glycation, can also adversely affect ER function, leading to pathogenic ER stress, followed by the unfolded protein response. The concomitant presence of advanced glycation in the same conditions with ER stress suggests their crosstalk in the progression of diseases associated with hypoxic and oxidative stress.
Current data support the direct or indirect induction of ER stress response by advanced glycation end products or advanced glycation end product precursors in the pathogenesis of metabolic diseases. Inhibitors of advanced glycation acting as potent ER stress modulators with beneficial effects in restoring ER homeostasis and adjusting physiological unfolded protein response level present an emerging therapeutic approach with significant applications, especially in the context of metabolic dysfunction.
高级糖基化是蛋白质、DNA 和脂质的主要翻译后修饰，在氧化应激增加、高血糖和缺氧的情况下加速，导致各种代谢疾病，如糖尿病、肥胖症、炎症、多囊卵巢综合征、缺血性心血管疾病和神经退行性疾病。高级糖基化在内质网（ER）稳态中的潜在作用在很大程度上是未知的。
从 2000 年到 2011 年，在 PubMed 上搜索了关于高级糖基化和与代谢调节有关的 ER 应激的基础和临床同行评议文章。对相关的文章和引用的参考文献进行了综述。
最近的证据表明，高血糖、缺氧和氧化应激不仅会引发高级糖基化，还会对 ER 功能产生不利影响，导致致病性 ER 应激，随后是未折叠蛋白反应。在相同条件下，高级糖基化和 ER 应激同时存在，提示它们在与缺氧和氧化应激相关疾病的进展中存在相互作用。
目前的数据支持在代谢疾病的发病机制中，高级糖基化终产物或高级糖基化终产物前体直接或间接诱导 ER 应激反应。作为有效的 ER 应激调节剂，抑制高级糖基化的抑制剂在恢复 ER 稳态和调节生理未折叠蛋白反应水平方面具有有益的作用，这是一种具有重要应用前景的新兴治疗方法，尤其是在代谢功能障碍的背景下。
