کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
4330116 1614249 2008 9 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Glia maturation factor overexpression in neuroblastoma cells activates glycogen synthase kinase-3β and caspase-3
موضوعات مرتبط
علوم زیستی و بیوفناوری علم عصب شناسی علوم اعصاب (عمومی)
پیش نمایش صفحه اول مقاله
Glia maturation factor overexpression in neuroblastoma cells activates glycogen synthase kinase-3β and caspase-3
چکیده انگلیسی

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.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Brain Research - Volume 1190, 23 January 2008, Pages 206–214
نویسندگان
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