Nanosecond pulsed electric fields induce poly(ADP-ribose) formation and non-apoptotic cell death in HeLa S3 cells
Nanosecond pulsed electric fields induce poly(ADP-ribose) formation and non-apoptotic cell death in HeLa S3 cells
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DOI：
10.1016/j.bbrc.2013.07.083
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发表时间：
2013-08-30
影响因子：
3.1
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
纳秒脉冲电场（nsPEFs）最近由于其诱导细胞死亡的潜力而作为有效的癌症治疗而受到关注。先前的研究表明，细胞凋亡是几种细胞系（如Jurkat细胞）中nsPEF诱导的细胞死亡的主要模式。在这项研究中，我们分析了nsPEFs诱导细胞死亡的分子机制。当将nsPEFs应用于Jurkat细胞时，容易诱导细胞凋亡。接下来，我们使用HeLa S3细胞并分析凋亡事件。与我们的预期相反，nsPEF暴露的HeLa S3细胞没有表现出凋亡执行的分子迹象。相反，nsPEFs诱导形成聚（ADP-核糖）（PAR），这是坏死的标志。PAR形成与细胞活力降低同时发生，支持nsPEF诱导的PAR形成对细胞死亡的影响。已知坏死性PAR形成由聚（ADP-核糖）聚合酶-1（PARP-1）催化，凋亡细胞中的PARP-1通过半胱天冬酶介导的蛋白水解失活。因此，我们分别在nsPEF暴露和UV照射的细胞中观察到完整和切割形式的PARP-1。总之，nsPEFs以细胞类型特异性的方式诱导两种不同的细胞死亡模式，并且HeLa S3细胞响应于nsPEFs显示PAR相关的非凋亡性细胞死亡。(C)2013 Elsevier Inc. All rights reserved.
Nanosecond pulsed electric fields (nsPEFs) have recently gained attention as effective cancer therapy owing to their potency for cell death induction. Previous studies have shown that apoptosis is a predominant mode of nsPEF-induced cell death in several cell lines, such as Jurkat cells. In this study, we analyzed molecular mechanisms for cell death induced by nsPEFs. When nsPEFs were applied to Jurkat cells, apoptosis was readily induced. Next, we used HeLa S3 cells and analyzed apoptotic events. Contrary to our expectation, nsPEF-exposed HeLa S3 cells exhibited no molecular signs of apoptosis execution. Instead, nsPEFs induced the formation of poly(ADP-ribose) (PAR), a hallmark of necrosis. PAR formation occurred concurrently with a decrease in cell viability, supporting implications of nsPEF-induced PAR formation for cell death. Necrotic PAR formation is known to be catalyzed by poly(ADP-ribose) polymerase-1 (PARP-1), and PARP-1 in apoptotic cells is inactivated by caspase-mediated proteolysis. Consistently, we observed intact and cleaved forms of PARP-1 in nsPEF-exposed and UV-irradiated cells, respectively. Taken together, nsPEFs induce two distinct modes of cell death in a cell type-specific manner, and HeLa S3 cells show PAR-associated non-apoptotic cell death in response to nsPEFs. (C) 2013 Elsevier Inc. All rights reserved.