Takadera T, Sakamoto Y, Hizume Y, Ohyashiki T
Department of Clinical Chemistry, Faculty of Pharmaceutical Sciences, Hokuriku University, Ho-3, Kanagawa-machi, Kanazawa, Ishikawa, 920-1148, Japan.
Cell Biol Toxicol. 2007 Sep;23(5):355-60. doi: 10.1007/s10565-007-0192-7. Epub 2007 Mar 24.
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.
本研究的目的是使用糖原合酶激酶（GSK）抑制剂来检测GSK-3是否参与环孢素A（CsA）和FK506诱导的PC12细胞凋亡。CsA和FK506增加了凋亡细胞死亡，并伴有细胞收缩以及核浓缩或核碎裂等形态学变化。神经生长因子（NGF）完全阻断了细胞死亡。半胱天冬酶-3的激活伴随着CsA和FK506诱导的细胞死亡，并被NGF抑制。GSK-3抑制剂如阿尔斯特波隆和SB216763可预防CsA和FK506诱导的凋亡。这些结果表明，CsA和FK506诱导半胱天冬酶依赖性凋亡，并且GSK-3的激活参与了CsA和FK506诱导的PC12细胞凋亡。
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