Hirszfeld Institute of Immunology and Experimental Therapy, Polish Academy of Sciences, Weigla 12, 53-114, Wrocław, Poland.
Centre for Interdisciplinary Research, The John Paul II Catholic University of Lublin, Konstantynow 1J, 20-708, Lublin, Poland.
Sci Rep. 2021 Feb 3;11(1):2940. doi: 10.1038/s41598-021-82585-7.
Non-enzymatic modification of proteins by carbohydrates, known as glycation, leads to generation of advanced glycation end-products (AGEs). In our study we used in vitro generated AGEs to model glycation in vivo. We discovered in vivo analogs of unusual melibiose-adducts designated MAGEs (mel-derived AGEs) synthesized in vitro under anhydrous conditions with bovine serum albumin and myoglobin. Using nuclear magnetic resonance spectroscopy we have identified MAGEs as a set of isomers, with open-chain and cyclic structures, of the fructosamine moiety. We generated a mouse anti-MAGE monoclonal antibody and show for the first time that the native and previously undescribed analogous glycation product exists in living organisms and is naturally present in tissues of both invertebrates and vertebrates, including humans. We also report MAGE cross-reactive auto-antibodies in patients with diabetes. We anticipate our approach for modeling glycation in vivo will be a foundational methodology in cell biology. Further studies relevant to the discovery of MAGE may contribute to clarifying disease mechanisms and to the development of novel therapeutic options for diabetic complications, neuropathology, and cancer.
非酶糖基化修饰蛋白质，被称为糖基化，导致晚期糖基化终末产物（AGEs）的产生。在我们的研究中，我们使用体外生成的 AGEs 来模拟体内的糖基化。我们在无水条件下，使用牛血清白蛋白和肌红蛋白，在体外合成了一种不寻常的棉子糖加合物的体内类似物，命名为 MAGEs（来源于棉子糖的 AGEs）。我们利用核磁共振波谱学，鉴定出 MAGEs 是一系列具有开链和环状结构的果糖胺部分的异构体。我们生成了一种抗 MAGE 的小鼠单克隆抗体，并首次表明天然的、以前未被描述的类似糖基化产物存在于生物体中，并且在无脊椎动物和脊椎动物（包括人类）的组织中自然存在。我们还报告了糖尿病患者中存在 MAGE 交叉反应性自身抗体。我们预计我们的体内糖基化建模方法将成为细胞生物学中的基础方法。与 MAGE 发现相关的进一步研究可能有助于阐明疾病机制，并为糖尿病并发症、神经病理学和癌症的新型治疗选择提供依据。
