Abstract：
Glycation is a non-enzymatic posttranslational modification coming from the reaction between reducing sugars and free amino groups in proteins, where early glycation products (fructosyl-lysine, FL) and advanced glycation end products (AGEs) are formed. The occurrence of glycation and accumulation of AGEs have been closely associated with hepatocellular carcinoma (HCC). Here, we reported the characterization of differential glycation in HCC using tissue proteomics with stable isotopic labeling; early glycation-modified peptides were enriched with boronate affinity chromatography (BAC), and AGEs-modified peptides were fractionated with basic reversed-phase separation. By this integrated approach, 3717 and 1137 early and advanced glycated peptides corresponding to 4007 sites on 1484 proteins were identified with a false discovery rate (FDR) of no more than 1%. One hundred fifty-five sites were modified with both early and advanced end glycation products. Five early and 7 advanced glycated peptides were quantified to be differentially expressed in HCC tissues relative to paired adjacent tissues. Most (8 out of 10) of the proteins corresponding to the differential glycated peptides have previously been reported with dysregulation in HCC. The results together may deepen our knowledge of glycation as well as provide insights for therapeutics.
摘要：
糖基化是一种非酶翻译后修饰，来自蛋白质中还原糖和游离氨基之间的反应，早期糖基化产物（果糖基赖氨酸，FL)和晚期糖基化终产物(AGEs)形成。糖基化和AGEs的积累与肝细胞癌（HCC）的发生密切相关。这里,我们报道了使用具有稳定同位素标记的组织蛋白质组学在HCC中的差异糖基化的表征;早期糖基化修饰的肽用硼酸酯亲和色谱（BAC）富集，和AGEs修饰的肽用碱性反相分离进行分馏。通过这种综合方法，以不超过1%的错误发现率(FDR)鉴定对应于1484种蛋白质上4007位点的3717和1137种早期和晚期糖基化肽。一百五十五个位点用早期和晚期末端糖基化产物修饰。5种早期和7种晚期糖基化肽被定量为相对于配对的邻近组织在HCC组织中差异表达。先前已经报道了对应于差异糖化肽的大多数(10个中的8个)蛋白质在HCC中具有失调。这些结果可以加深我们对糖基化的了解，并为治疗提供见解。
