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

Abstract

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 H2 O2 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 H2 O2 -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.

• Authors: Emese Kátai, József Pál, Viktor Soma Poór, Rupeena Purewal, Attila Miseta, Tamás Nagy
• Journal: Journal of cellular and molecular medicine (J Cell Mol Med) Vol. 20 Issue 12 Pg. 2269-2277 (12 2016) ISSN: 1582-4934 [Electronic] England
• PMID: 27456536 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2016 The Authors. Journal of Cellular and Molecular Medicine published by John Wiley & Sons Ltd and Foundation for Cellular and Molecular Medicine.

Chemical References

• RNA, Messenger
• tau Proteins
• Hydrogen Peroxide
• N-Acetylglucosaminyltransferases
• Nitrogenous Group Transferases
• Acetylglucosamine

Topics

• Acetylglucosamine (metabolism)
• Cell Line, Tumor
• Cell Survival (drug effects)
• Fluorescent Antibody Technique
• Glycosylation (drug effects)
• Humans
• Hydrogen Peroxide (toxicity)
• N-Acetylglucosaminyltransferases (genetics, metabolism)
• Nitrogenous Group Transferases (genetics, metabolism)
• Oxidative Stress (drug effects)
• Phosphorylation (drug effects)
• RNA, Messenger (genetics, metabolism)
• Real-Time Polymerase Chain Reaction
• Time Factors
• tau Proteins (metabolism)