Oxidative stress induces transient O-Glc NAc elevation and tau dephosphorylation in SH- SY5Y cells.

O-linked β- N-acetlyglucosamine or O-Glc NAc modification is a dynamic post-translational modification occurring on the Ser/Thr residues of many intracellular proteins. The chronic imbalance between phosphorylation and O-Glc NAc on tau protein is considered as one of the main hallmarks of Alzheimer's disease. In recent years, many studies also showed that O-Glc NAc 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-Glc NAc after treatment with 0.5 mM H₂O₂ for 30 min. to induce oxidative stress. We found that overall O-Glc NAc 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-Glc NAc modification after H₂O₂-induced oxidative stress is detectable in cells of neuronal origin. Furthermore, oxidative stress changes the dynamic balance between O-Glc NAc and phosphorylation on tau proteins. [ABSTRACT FROM AUTHOR]