Oxidative stress induces transient O‐Glc NA c elevation and tau dephosphorylation in SH ‐ SY 5Y cells

O‐linked β‐ N ‐acetlyglucosamine or O‐Glc NA c 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 NA c 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 NA c 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 ‐ SY 5Y we investigated the dynamic nature of O‐Glc NA c after treatment with 0.5 mM H 2 O 2 for 30 min. to induce oxidative stress. We found that overall O‐Glc NA c 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 PHF 1 sites showed inverse dynamic to O‐Glycosylation. In conclusion, our results show that temporary elevation in O‐Glc NA c modification after H 2 O 2 ‐induced oxidative stress is detectable in cells of neuronal origin. Furthermore, oxidative stress changes the dynamic balance between O‐Glc NA c and phosphorylation on tau proteins.