Glia maturation factor overexpression in neuroblastoma cells activates glycogen synthase kinase-3β and caspase-3

Asgar Zaheer; Scott Knight; Ashna Zaheer; Marcus Ahrens; Shailendra K. Sahu; Baoli Yang

doi:10.1016/j.brainres.2007.11.011

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Glia maturation factor overexpression in neuroblastoma cells activates glycogen synthase kinase-3β and caspase-3

Journal article

Peer reviewed

Glia maturation factor overexpression in neuroblastoma cells activates glycogen synthase kinase-3β and caspase-3

Asgar Zaheer, Scott Knight, Ashna Zaheer, Marcus Ahrens, Shailendra K. Sahu and Baoli Yang

Brain research, Vol.1190, pp.206-214

01/23/2008

DOI: 10.1016/j.brainres.2007.11.011

PMCID: PMC2343001

PMID: 18054898

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Abstract

In the present study we report that a replication-defective adenovirus construct of GMF cDNA (GMF-V) induced overexpression of GMF protein in neuroblastoma (N18) cells caused cytotoxicity and loss of cell viability. A significant increase in activation of GSK-3β occurred after infection with GMF-V when compared with mock and lacZ controls. Overexpression of GMF also increased caspase-3 activity, an early marker of apoptosis. Depletion of GMF gene by introducing GMF-specific siRNA (GsiRNA) completely blocked both activation of GSK-3β and caspase-3 activation whereas a control scrambled siRNA (CsiRNA) had no effect. A cell-permeable peptide inhibitor of GSK-3β, and lithium completely prevented GMF-dependent activation of caspase-3. These results demonstrate that GSK-3 mediates activation of the death domain caspase by GMF overexpression. We also show that the phosphorylation of GSK-3-dependent site of Tau was a consequence of GMF-overexpression in N18 cells. Taken together our results imply that GMF is involved in the signaling leading to the activation of GSK-3β and caspase-3 in N18 cells and strongly suggest its involvement in neurodegeneration since GSK-3β is known to hyperphosphorylate tau which is associated with the neurotoxicity of neurofibrillary tangles in Alzheimer's disease.

Obstetrics and Gynecology

Details

Title: Subtitle: Glia maturation factor overexpression in neuroblastoma cells activates glycogen synthase kinase-3β and caspase-3
Creators: Asgar Zaheer
Scott Knight
Ashna Zaheer
Marcus Ahrens
Shailendra K. Sahu
Baoli Yang - University of Iowa
Resource Type: Journal article
Publication Details: Brain research, Vol.1190, pp.206-214
DOI: 10.1016/j.brainres.2007.11.011
PMID: 18054898
PMCID: PMC2343001
NLM abbreviation: Brain Res
ISSN: 0006-8993
eISSN: 1872-6240
Publisher: Elsevier BV
Copyright: Elsevier B.V.
Language: English
Date published: 01/23/2008
Academic Unit: Neurology; BioVentures Center; Obstetrics and Gynecology
Record Identifier: 9983557775502771

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