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Article: In vivo activation and nuclear translocation of phosphorylated glycogen synthase kinase-3β in neuronal apoptosis: Links to tau phosphorylation

TitleIn vivo activation and nuclear translocation of phosphorylated glycogen synthase kinase-3β in neuronal apoptosis: Links to tau phosphorylation
Authors
Issue Date2002
PublisherBlackwell Publishing Ltd. The Journal's web site is located at http://www.blackwellpublishing.com/journals/EJN
Citation
European Journal Of Neuroscience, 2002, v. 15 n. 4, p. 651-660 How to Cite?
AbstractThe roles of glycogen synthase kinase-3β (GSK-3β) and tau phosphorylation were examined in seven-day-old rats injected with the NMDA receptor antagonist (MK801) that is known to induce neuronal apoptosis. Immunoblot and immunohistochemical analysis of brain samples demonstrated a site-specific increase in tau phosphorylation associated with the relocalization of the protein to the nuclear/perinuclear region of apoptotic neurons. In addition, a tau 32-kDa fragment was detected, suggesting that tau was a target of intracellular proteolysis in MK801-treated brains. The proteolytically modified form of tau has reduced ability to bind to microtubules. GSK-3β kinase assay and immunoblottings of active (tyrosine-216) and inactive (serine-9) forms of GSK-3β revealed a rapid and transient increase in the kinase activity. Lithium chloride, a GSK-3β inhibitor, prevented tau phosphorylation suggesting that tau phosphorylation is mediated by the activation of GSK-3β. Confocal microscopy using double labelling of tau and GSK-3β revealed that the activation of GSK-3β in neurons was associated with early (2 h) nuclear translocation of tyrosine-216 GSK-3β. The execution phase of neuronal apoptosis was accompanied by a selective phosphorylation of serine-9 and dephosphorylation of tyrosine-216 GSK-3β. These findings demonstrate that in vivo, GSK-3β kinase activation and nuclear translocation are early stress signals of neuronal apoptosis.
Persistent Identifierhttp://hdl.handle.net/10722/147511
ISSN
2015 Impact Factor: 2.975
2015 SCImago Journal Rankings: 2.130
ISI Accession Number ID
References

 

DC FieldValueLanguage
dc.contributor.authorElyaman, Wen_US
dc.contributor.authorTerro, Fen_US
dc.contributor.authorWong, NSen_US
dc.contributor.authorHugon, Jen_US
dc.date.accessioned2012-05-29T06:04:15Z-
dc.date.available2012-05-29T06:04:15Z-
dc.date.issued2002en_US
dc.identifier.citationEuropean Journal Of Neuroscience, 2002, v. 15 n. 4, p. 651-660en_US
dc.identifier.issn0953-816Xen_US
dc.identifier.urihttp://hdl.handle.net/10722/147511-
dc.description.abstractThe roles of glycogen synthase kinase-3β (GSK-3β) and tau phosphorylation were examined in seven-day-old rats injected with the NMDA receptor antagonist (MK801) that is known to induce neuronal apoptosis. Immunoblot and immunohistochemical analysis of brain samples demonstrated a site-specific increase in tau phosphorylation associated with the relocalization of the protein to the nuclear/perinuclear region of apoptotic neurons. In addition, a tau 32-kDa fragment was detected, suggesting that tau was a target of intracellular proteolysis in MK801-treated brains. The proteolytically modified form of tau has reduced ability to bind to microtubules. GSK-3β kinase assay and immunoblottings of active (tyrosine-216) and inactive (serine-9) forms of GSK-3β revealed a rapid and transient increase in the kinase activity. Lithium chloride, a GSK-3β inhibitor, prevented tau phosphorylation suggesting that tau phosphorylation is mediated by the activation of GSK-3β. Confocal microscopy using double labelling of tau and GSK-3β revealed that the activation of GSK-3β in neurons was associated with early (2 h) nuclear translocation of tyrosine-216 GSK-3β. The execution phase of neuronal apoptosis was accompanied by a selective phosphorylation of serine-9 and dephosphorylation of tyrosine-216 GSK-3β. These findings demonstrate that in vivo, GSK-3β kinase activation and nuclear translocation are early stress signals of neuronal apoptosis.en_US
dc.languageengen_US
dc.publisherBlackwell Publishing Ltd. The Journal's web site is located at http://www.blackwellpublishing.com/journals/EJNen_US
dc.relation.ispartofEuropean Journal of Neuroscienceen_US
dc.subject.meshActive Transport, Cell Nucleus - Drug Effects - Physiologyen_US
dc.subject.meshAnimalsen_US
dc.subject.meshAnimals, Newbornen_US
dc.subject.meshApoptosis - Drug Effects - Physiologyen_US
dc.subject.meshBrain - Cytology - Enzymology - Growth & Developmenten_US
dc.subject.meshCalcium-Calmodulin-Dependent Protein Kinases - Drug Effects - Metabolismen_US
dc.subject.meshCell Compartmentation - Drug Effects - Physiologyen_US
dc.subject.meshCell Nucleus - Drug Effects - Enzymology - Ultrastructureen_US
dc.subject.meshCytoplasm - Drug Effects - Enzymology - Ultrastructureen_US
dc.subject.meshCytoskeleton - Drug Effects - Metabolismen_US
dc.subject.meshExcitatory Amino Acid Antagonists - Pharmacologyen_US
dc.subject.meshFemaleen_US
dc.subject.meshGlycogen Synthase Kinase 3en_US
dc.subject.meshGlycogen Synthase Kinasesen_US
dc.subject.meshMaleen_US
dc.subject.meshNerve Degeneration - Chemically Induced - Metabolism - Physiopathologyen_US
dc.subject.meshNeurons - Cytology - Drug Effects - Enzymologyen_US
dc.subject.meshPeptide Fragments - Drug Effects - Metabolismen_US
dc.subject.meshPhosphorylation - Drug Effectsen_US
dc.subject.meshRatsen_US
dc.subject.meshRats, Wistaren_US
dc.subject.meshReceptors, N-Methyl-D-Aspartate - Antagonists & Inhibitors - Metabolismen_US
dc.subject.meshStress, Physiological - Chemically Induced - Enzymology - Physiopathologyen_US
dc.subject.meshTau Proteins - Drug Effects - Metabolismen_US
dc.titleIn vivo activation and nuclear translocation of phosphorylated glycogen synthase kinase-3β in neuronal apoptosis: Links to tau phosphorylationen_US
dc.typeArticleen_US
dc.identifier.emailWong, NS:nswong@hkucc.hku.hken_US
dc.identifier.authorityWong, NS=rp00340en_US
dc.description.naturelink_to_subscribed_fulltexten_US
dc.identifier.doi10.1046/j.1460-9568.2002.01899.xen_US
dc.identifier.pmid11886446-
dc.identifier.scopuseid_2-s2.0-18744385488en_US
dc.identifier.hkuros114929-
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-18744385488&selection=ref&src=s&origin=recordpageen_US
dc.identifier.volume15en_US
dc.identifier.issue4en_US
dc.identifier.spage651en_US
dc.identifier.epage660en_US
dc.identifier.isiWOS:000174693700007-
dc.publisher.placeUnited Kingdomen_US
dc.identifier.scopusauthoridElyaman, W=6603236614en_US
dc.identifier.scopusauthoridTerro, F=6602670596en_US
dc.identifier.scopusauthoridWong, NS=7202836641en_US
dc.identifier.scopusauthoridHugon, J=7103202992en_US

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