期刊
NEUROSCIENCE LETTERS
卷 408, 期 2, 页码 124-128出版社
ELSEVIER IRELAND LTD
DOI: 10.1016/j.neulet.2006.08.066
关键词
calcium; thapsigargin; glycogen synthase kinase-3; caspase-3; apoptosis; PC12 cells
Uncontrolled calcium stress has been linked causally to a variety of neurodegenerative diseases, including ischemia, excitotoxicity and Alzheimer's disease. Thapsigargin, which increases [Ca2+](i), induces apoptotic cell death (chromatin condensation and DNA fragmentation) accompanied by caspase-3 activation in PC12 cells. We examined whether GSK-3 is involved in thapsigargain-induced cell death by using GSK-3 inhibitors in PC12 cells. Cells treated with 0.1 mu M thapsigargin for 24 It shrank. The injured cells underwent chromatin condensation and nuclear fragmentation, indicating apoptotic cell death. We assayed the effects of selective GSK-3 inhibitors, SB216763, azakenpaullone and alsteropaullone on thapsigargin-induced apoptosis. These inhibitors completely protected cells from thapsigargin-induced apoptosis. Alsterpaullone did not reduce the GRP78 protein expression induced by thapsigargin, suggesting that GSK-3 activation is not involved in induction of GRP78. In addition, GSK-3 inhibitors inhibited caspase-3 activation accompanied by thapsigargin-induced apoptosis. We showed in this report that thapsigargin-induced apoptosis is prevented by GSK-3 inhibitors, suggesting that thapsigargin induces caspase-dependent apoptosis mediated through GSK-3 activation in PC 12 cells. (c) 2006 Elsevier Ireland Ltd. All rights reserved.
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