Kátai Emese, Pál József, Poór Viktor Soma, Purewal Rupeena, Miseta Attila, Nagy Tamás
Department of Laboratory Medicine, University of Pécs, Pécs, Hungary.
Department of Neurosurgery, University of Pécs, Pécs, Hungary.
J Cell Mol Med. 2016 Dec;20(12):2269-2277. doi: 10.1111/jcmm.12910. Epub 2016 Jul 26.
O-linked β-N-acetlyglucosamine or O-GlcNAc modification is a dynamic post-translational modification occurring on the Ser/Thr residues of many intracellular proteins. The chronic imbalance between phosphorylation and O-GlcNAc on tau protein is considered as one of the main hallmarks of Alzheimer's disease. In recent years, many studies also showed that O-GlcNAc levels can elevate upon acute stress and suggested that this might facilitate cell survival. However, many consider chronic stress, including oxidative damage as a major risk factor in the development of the disease. In this study, using the neuronal cell line SH-SY5Y we investigated the dynamic nature of O-GlcNAc after treatment with 0.5 mM H O for 30 min. to induce oxidative stress. We found that overall O-GlcNAc quickly increased and reached peak level at around 2 hrs post-stress, then returned to baseline levels after about 24 hrs. Interestingly, we also found that tau protein phosphorylation at site S262 showed parallel, whereas at S199 and PHF1 sites showed inverse dynamic to O-Glycosylation. In conclusion, our results show that temporary elevation in O-GlcNAc modification after H O -induced oxidative stress is detectable in cells of neuronal origin. Furthermore, oxidative stress changes the dynamic balance between O-GlcNAc and phosphorylation on tau proteins.
O-连接的β-N-乙酰葡糖胺或O-GlcNAc修饰是一种发生在许多细胞内蛋白质丝氨酸/苏氨酸残基上的动态翻译后修饰。tau蛋白上磷酸化和O-GlcNAc之间的长期失衡被认为是阿尔茨海默病的主要标志之一。近年来，许多研究还表明，急性应激时O-GlcNAc水平会升高，并表明这可能促进细胞存活。然而，许多人认为包括氧化损伤在内的慢性应激是该疾病发展的主要危险因素。在本研究中，我们使用神经元细胞系SH-SY5Y，在用0.5 mM H₂O₂处理30分钟以诱导氧化应激后，研究了O-GlcNAc的动态变化。我们发现，总体上O-GlcNAc迅速增加，并在应激后约2小时达到峰值水平，然后在约24小时后恢复到基线水平。有趣的是，我们还发现tau蛋白在S262位点的磷酸化表现出平行变化，而在S199和PHF1位点则表现出与O-糖基化相反的动态变化。总之，我们的结果表明，在H₂O₂诱导的氧化应激后，神经元来源的细胞中可检测到O-GlcNAc修饰的暂时升高。此外，氧化应激改变了tau蛋白上O-GlcNAc和磷酸化之间的动态平衡。
