These tools will no longer be maintained as of December 31, 2024. Archived website can be found here. PubMed4Hh GitHub repository can be found here. Contact NLM Customer Service if you have questions.


Pubmed for Handhelds

PUBMED FOR HANDHELDS

Search MEDLINE/PubMed

  • Title: In vivo activation and nuclear translocation of phosphorylated glycogen synthase kinase-3beta in neuronal apoptosis: links to tau phosphorylation.
    Author: Elyaman W, Terro F, Wong NS, Hugon J.
    Journal: Eur J Neurosci; 2002 Feb; 15(4):651-60. PubMed ID: 11886446.
    Abstract:
    The roles of glycogen synthase kinase-3beta (GSK-3beta) 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-3beta kinase assay and immunoblottings of active (tyrosine-216) and inactive (serine-9) forms of GSK-3beta revealed a rapid and transient increase in the kinase activity. Lithium chloride, a GSK-3beta inhibitor, prevented tau phosphorylation suggesting that tau phosphorylation is mediated by the activation of GSK-3beta. Confocal microscopy using double labelling of tau and GSK-3beta revealed that the activation of GSK-3beta in neurons was associated with early (2 h) nuclear translocation of tyrosine-216 GSK-3beta. The execution phase of neuronal apoptosis was accompanied by a selective phosphorylation of serine-9 and dephosphorylation of tyrosine-216 GSK-3beta. These findings demonstrate that in vivo, GSK-3beta kinase activation and nuclear translocation are early stress signals of neuronal apoptosis.
    [Abstract] [Full Text] [Related] [New Search]