Τίτλος:
Oxygen and Glucose Deprivation Alter Synaptic Distribution of Tau Protein: The Role of Phosphorylation
Γλώσσες Τεκμηρίου:
Αγγλικά
Περίληψη:
Alterations in tau synaptic distribution are considered to underlie synaptic dysfunction observed in Alzheimer's disease (AD). In the present study, brain blood hypoperfusion was simulated in mouse brain slices, and tau levels and phosphorylation were investigated in total extracts, as well as in postsynaptic density fractions (PSDs) and non-PSDs obtained through differential extraction and centrifugation. Oxygen deprivation (OD) resulted in tau dephosphorylation at several AD-related residues and activation of GSK3β and phosphatase PP2A. On the contrary, glucose deprivation (GD) did not affect total levels of cellular tau or its phosphorylation despite inactivation of GSK3β. However, tau distribution in PSD and non-PSD fractions and the pattern of tau phosphorylation in these compartments is highly complex. In PSDs, tau was increased under GD conditions and decreased under OD conditions. GD resulted in tau dephosphorylation at Ser199, Ser262, and Ser396 while OD resulted in tau hyperphosphorylation at Ser199 and Ser404. In the non-PSD fraction, GD or OD resulted in lower levels of tau, but the phosphorylation status of tau was differentially affected. In GD conditions, tau was found dephosphorylated at Ser199, Thr205, and Ser404 and hyperphosphorylated at Ser262. However, in OD conditions tau was found hyperphosphorylated at Thr205, SerSer356, Ser396, and Ser404. Combined OD and GD resulted in degradation of cellular tau and dephosphorylation of PSD tau at Ser396 and Ser404. These results indicate that oxygen deprivation causes dephosphorylation of tau, while GD and OD differentially affect distribution of total tau and tau phosphorylation variants in neuronal compartments by activating different mechanisms. © 2017 - IOS Press and the authors. All rights reserved.
Συγγραφείς:
Mavroeidi, P.
Mavrofrydi, O.
Pappa, E.
Panopoulou, M.
Papazafiri, P.
Haralambous, S.
Efthimiopoulos, S.
Περιοδικό:
Journal of Alzheimer's disease : JAD
Λέξεις-κλειδιά:
glycogen synthase kinase 3beta; phosphoprotein phosphatase 2A; tau protein; glucose; glucose transporter 3; glycogen synthase kinase 3beta; phosphoprotein phosphatase 2; serine; Slc2a3 protein, mouse; tau protein, animal cell; animal experiment; animal model; animal tissue; Article; brain blood flow; brain cortex slice; brain ischemia; brain perfusion; cell fractionation; cellular distribution; controlled study; enzyme activation; hypoglycemia; mouse; nonhuman; postsynaptic density; priority journal; protein degradation; protein dephosphorylation; protein phosphorylation; synapse; animal; brain cortex; C57BL mouse; cell culture; cytology; deficiency; dose response; drug effects; genetics; hypoxia; metabolism; nerve cell; pathology; phosphorylation; transgenic mouse, Animals; Cells, Cultured; Cerebral Cortex; Dose-Response Relationship, Drug; Glucose; Glucose Transporter Type 3; Glycogen Synthase Kinase 3 beta; Hypoxia; Mice; Mice, Inbred C57BL; Mice, Transgenic; Neurons; Phosphorylation; Protein Phosphatase 2; Serine; Subcellular Fractions; Synapses; tau Proteins
