Different involvement of extracellular calcium in two modes of cell death induced by nanosecond pulsed electric fields
Different involvement of extracellular calcium in two modes of cell death induced by nanosecond pulsed electric fields
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DOI：
10.1016/j.abb.2014.05.020
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发表时间：
2014-08-01
影响因子：
3.9
通讯作者：
Yano, Ken-ichi
中科院分区：
文献类型：
--
作者：
Morotomi-Yano, Keiko;Akiyama, Hidenori;Yano, Ken-ichi
将培养的细胞暴露于纳秒脉冲电场（nsPEFs）诱导各种细胞反应，包括细胞外Ca 2+的内流和细胞死亡。近年来，nsPEFs被认为是一种新型的肿瘤治疗手段，但其分子作用机制仍有待充分阐明。在这里，我们证明了细胞外Ca 2+参与nsPEF诱导的细胞死亡。细胞外Ca ~（2+）对HeLa S3细胞的坏死和随后的聚腺苷二磷酸核糖（PAR）形成是必不可少的。用Ca 2+离子载体处理增强了nsPEF暴露的HeLa S3细胞的坏死以及PAR形成。在细胞外Ca 2+的情况下，HeLa S3细胞对nsPEFs不太敏感，并表现出caspase 3和PARP-1的凋亡蛋白水解。HeLa S3细胞即使在nsPEF暴露后也保留了经历凋亡的能力，但相反经历了坏死，这表明坏死是细胞死亡的优先模式。在K562和HEK 293细胞中，暴露于nsPEFs导致形成坏死相关的PAR，而Jurkat细胞只经历凋亡独立于细胞外Ca 2+。这些观察结果表明，由nsPEFs诱导的细胞死亡的模式是细胞类型依赖性的，并且细胞外Ca 2+是nsPEFs诱导的坏死的关键因素。(C)2014 Elsevier Inc. All rights reserved.
Exposure of cultured cells to nanosecond pulsed electric fields (nsPEFs) induces various cellular responses, including the influx of extracellular Ca2+ and cell death. Recently, nsPEFs have been regarded as a novel means of cancer therapy, but their molecular mechanism of action remains to be fully elucidated. Here, we demonstrate the involvement of extracellular Ca2+ in nsPEF-induced cell death. Extracellular Ca2+ was essential for necrosis and consequent poly(ADP-ribose) (PAR) formation in HeLa S3 cells. Treatment with a Ca2+ ionophore enhanced necrosis as well as PAR formation in nsPEF-exposed HeLa S3 cells. In the absence of extracellular Ca2+, HeLa S3 cells were less susceptible to nsPEFs and exhibited apoptotic proteolysis of caspase 3 and PARP-1. HeLa S3 cells retained the ability to undergo apoptosis even after nsPEF exposure but instead underwent necrosis, suggesting that necrosis is the preferential mode of cell death. In K562 and HEK293 cells, exposure to nsPEFs resulted in the formation of necrosis-associated PAR, whereas Jurkat cells exclusively underwent apoptosis independently of extracellular Ca2+. These observations demonstrate that the mode of cell death induced by nsPEFs is cell-type dependent and that extracellular Ca2+ is a critical factor for nsPEF-induced necrosis. (C) 2014 Elsevier Inc. All rights reserved.