Mitochondrial dysfunction is related to necrosis-like programmed cell death induced by A23187 in CEM cells
Mitochondrial dysfunction is related to necrosis-like programmed cell death induced by A23187 in CEM cells
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DOI：
10.1016/j.ejphar.2005.04.018
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发表时间：
2005-06-15
影响因子：
5
通讯作者：
Nakahata, T
中科院分区：
文献类型：
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作者：
Hamahata, K;Adachi, S;Nakahata, T
我们以前曾报道，钙离子载体A23187差异诱导CEM细胞，T-淋巴细胞白血病细胞系的坏死，和HL 60细胞，早幼粒细胞白血病细胞系的凋亡。然而，用VP 16刺激在两种细胞百合中诱导典型的凋亡。CEM细胞在处理后5分钟内开始坏死，其特征为细胞皱缩和聚集。电子显微镜下可见线粒体肿胀、荧光染色质凝聚和质膜完整。CEM细胞中的这些A23187-照射的变化被氯硝西泮或CGP 37157（线粒体Na+/Ca ~（2+）交换抑制剂）抑制。然而，这些变化不受环孢菌素A（线粒体通透性转换孔抑制剂）的影响。在CEM和HL 60细胞中，用2 μ M A23187处理1分钟内，细胞内钙以相似幅度增加。在CEM和HL 60细胞中，单独用氯硝西泮预处理，线粒体内钙增加。然而，无论是未经处理还是用氯硝西泮预处理，PEM或HL 60细胞中的线粒体内钙并未因A23187而发生显着变化。A23187诱导CEM细胞坏死，同时线粒体功能障碍，这是独立的线粒体通透性转换，但受线粒体内钙，而HL 60细胞缺乏这些早期的变化。这两种细胞百合对A23187反应的差异可能来自线粒体膜对细胞内钙快速增加的敏感性的差异。(c)2005 Elsevier B.V保留所有权利。
We have previously reported that calcium ionophore A23187 differentially induces necrosis in CEM cells, a T-lymphoblastic leukemia cell line, and apoptosis in HL60 cells, a promyclocytic leukemia cell line. Stimulation with VP16, however, induces typical apoptosis in both cell lilies. Necrosis in CEM cells, characterizedby cell shrinkage and clustering, began within 5 min of treatment. Swelling of the mitochondria, lumpy chromatin condensation and intact plasma membranes were evident by electron microscopy. These A23187-illediated changes in CEM cells were suppressed by clonazepam or CGP37157, inhibitors of the mitochondrial Na+/Ca2+ exchanger. The changes, however, were not affected by cyclosporin A, an inhibitor of the mitochondrial permeability transition pore. In both CEM and HL60 cells, intra-cellular calcium increased with similar amplitude within 1 min of treatment with 2 mu M A23187. Intra-mitochondrial calcium increased with clonazepam pre-treatment alone in both CEM and HL60 cells. However, intra-mitochondrial calcium did not change drastically in response to A23187 in CEM or HL60 cells, either untreated or pre-treated with clonazepam. A23187 induces necrosis in CEM cells concurrent with mitochondrial dysfunction, which is independent of the mitochondrial permeability transition, but affected by intra-mitochondrial calcium, while HL60 cells lack these early changes. Differences in the responses to A23187 between these two cell lilies might derive from differences in the susceptibility of the mitochondrial membrane to rapid increases in intra-cellular calcium. (c) 2005 Elsevier B.V All rights reserved.