title: 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 H2O2for 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 H2O2-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.affiliation: Department of Laboratory Medicine, University of Pécs, Pécs, Hungary.
authors.forename: Emese
authors.initials: E
authors.lastname: Kátai
authors.affiliation: Department of Neurosurgery, University of Pécs, Pécs, Hungary.|Neuronal Networks Group, College of Medical and Dental Sciences, University of Birmingham, Birmingham, UK.
authors.forename: József
authors.initials: J
authors.lastname: Pál
authors.affiliation: Department of Forensic Medicine, University of Pécs, Pécs, Hungary.
authors.forename: Viktor Soma
authors.initials: VS
authors.lastname: Poór
authors.affiliation: Department of Pediatrics, West Virginia University, Morgantown, WV, USA.
authors.forename: Rupeena
authors.initials: R
authors.lastname: Purewal
authors.affiliation: Department of Laboratory Medicine, University of Pécs, Pécs, Hungary.
authors.forename: Attila
authors.initials: A
authors.lastname: Miseta
authors.affiliation: Department of Laboratory Medicine, University of Pécs, Pécs, Hungary.|János Szentágothai Research Centre, University of Pécs, Pécs, Hungary.
authors.forename: Tamás
authors.initials: T
authors.lastname: Nagy
mesh_terms: D000117:Acetylglucosamine / Q000378:metabolism*; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D005455:Fluorescent Antibody Technique; D006031:Glycosylation / Q000187:drug effects; D006801:Humans; D006861:Hydrogen Peroxide / Q000633:toxicity; D017351:N-Acetylglucosaminyltransferases / Q000235:genetics / Q000378:metabolism; D019884:Nitrogenous Group Transferases / Q000235:genetics / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects; D010766:Phosphorylation / Q000187:drug effects; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D060888:Real-Time Polymerase Chain Reaction; D013997:Time Factors; D016875:tau Proteins / Q000378:metabolism*
chemical_list: D012333:RNA, Messenger; D016875:tau Proteins; D006861:Hydrogen Peroxide; D017351:N-Acetylglucosaminyltransferases; D019884:Nitrogenous Group Transferases; D000117:Acetylglucosamine
keywords: Alzheimer's disease; O-GlcNAc; oxidative stress; stress response; tau phosphorylation