Bioelectrics Research Center, Kumamoto University, Kumamoto 860-8555, Japan.
Biochem Biophys Res Commun. 2011 May 13;408(3):471-6. doi: 10.1016/j.bbrc.2011.04.056. Epub 2011 Apr 19.
Nanosecond pulsed electric fields (nsPEFs) are increasingly recognized as a novel and unique tool in various life science fields, including electroporation and cancer therapy, although their mode of action in cells remains largely unclear. Here, we show that nsPEFs induce strong and transient activation of a signaling pathway involving c-Jun N-terminal kinase (JNK). Application of nsPEFs to HeLa S3 cells rapidly induced phosphorylation of JNK1 and MKK4, which is located immediately upstream of JNK in this signaling pathway. nsPEF application also elicited increased phosphorylation of c-Jun protein and dramatically elevated c-jun and c-fos mRNA levels. nsPEF-inducible events downstream of JNK were markedly suppressed by the JNK inhibitor SP600125, which confirmed JNK-dependency of these events in this pathway. Our results provide novel mechanistic insights into the mode of nsPEF action in human cells.
纳秒级电脉冲（nsPEFs）在包括电穿孔和癌症治疗在内的各种生命科学领域中，正日益被视为一种新颖而独特的工具，尽管其在细胞中的作用模式在很大程度上仍不清楚。在这里，我们表明 nsPEFs 诱导涉及 c-Jun N 端激酶（JNK）的信号通路的强烈和短暂激活。将 nsPEFs 应用于 HeLa S3 细胞可迅速诱导 JNK1 和 MKK4 的磷酸化，在该信号通路中，MKK4 位于 JNK 的上游。nsPEF 的应用还引起了 c-Jun 蛋白的磷酸化增加，并显著提高了 c-jun 和 c-fos mRNA 的水平。JNK 抑制剂 SP600125 显著抑制了 JNK 下游的 nsPEF 诱导事件，这证实了在该途径中这些事件对 JNK 的依赖性。我们的研究结果为 nsPEF 在人细胞中的作用模式提供了新的机制见解。
