Aguilar Aime Lopez, Hou Xiaomeng, Wen Liuqing, Wang Peng G, Wu Peng
Department of Molecular Medicine, The Scripps Research Institute, La Jolla, CA, 92037, USA.
Department of Chemistry, Georgia State University, Atlanta, Georgia, 30303, USA.
Chembiochem. 2017 Dec 14;18(24):2416-2421. doi: 10.1002/cbic.201700515. Epub 2017 Dec 5.
Modification of nuclear and cytoplasmic proteins by the addition or removal of O-GlcNAc dynamically impacts multiple biological processes. Here, we present the development of a chemoenzymatic histology method for the detection of O-GlcNAc in tissue specimens. We applied this method to screen murine organs, uncovering specific O-GlcNAc distribution patterns in different tissue structures. We then utilized our histology method for O-GlcNAc detection in human brain specimens from healthy donors and donors with Alzheimer's disease and found higher levels of O-GlcNAc in specimens from healthy donors. We also performed an analysis using a multiple cancer tissue array, uncovering different O-GlcNAc levels between healthy and cancerous tissues, as well as different O-GlcNAc cellular distributions within certain tissue specimens. This chemoenzymatic histology method therefore holds great potential for revealing the biology of O-GlcNAc in physiopathological processes.
通过添加或去除O - 连接的N - 乙酰葡糖胺(O - GlcNAc)对核蛋白和细胞质蛋白进行修饰,会动态影响多个生物学过程。在此,我们展示了一种用于检测组织标本中O - GlcNAc的化学酶组织学方法的开发。我们应用该方法筛选小鼠器官,揭示了不同组织结构中特定的O - GlcNAc分布模式。然后,我们利用这种组织学方法检测来自健康供体和患有阿尔茨海默病的供体的人脑标本中的O - GlcNAc,发现健康供体标本中的O - GlcNAc水平更高。我们还使用多种癌症组织阵列进行了分析,揭示了健康组织和癌组织之间不同的O - GlcNAc水平,以及某些组织标本内不同的O - GlcNAc细胞分布。因此,这种化学酶组织学方法在揭示生理病理过程中O - GlcNAc的生物学特性方面具有巨大潜力。