Cyclosporine A- and FK506-induced apoptosis in PC12 cells |
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Authors: | T Takadera Y Sakamoto Y Hizume T Ohyashiki |
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Institution: | (1) Department of Clinical Chemistry, Faculty of Pharmaceutical Sciences, Hokuriku University, Ho-3, Kanagawa-machi, Kanazawa Ishikawa, 920-1148, Japan |
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Abstract: | The purpose of this study was to examine, using glycogen synthase kinase (GSK) inhibitors, whether GSK-3 is involved in cyclosporine
A (CsA)- and FK506-induced apoptosis in PC12 cells. CsA and FK506 increased apoptotic cell death with morphological changes
characterized by cell shrinkage and nuclear condensation or fragmentation. Nerve growth factor (NGF) completely blocked cell
death. Caspase-3 activation was accompanied by CsA- and FK506-induced cell death and inhibited by NGF. GSK-3 inhibitors such
as alsterpaullone and SB216763 prevented CsA- and FK506-induced apoptosis. These results suggest that CsA and FK506 induce
caspase-dependent apoptosis and that GSK-3 activation is involved in CsA- and FK506-induced apoptosis in PC12 cells. |
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Keywords: | glycogen synthase kinase-3 cyclosporine A FK506 caspase apoptosis PC12 cells |
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