Nanosecond pulsed electric fields activate MAPK pathways in human cells

Application of nanosecond pulsed electric fields (nsPEFs) has attracted attention as a unique tool in life sciences, especially for cancer therapy, but the molecular mechanism of its action on living organisms is yet to be fully elucidated. Here, we report a transient activation of signaling pathways involving mitogen-activated protein kinases (MAPKs) by nsPEFs. Application of nsPEFs to HeLa S3 cells induced phosphorylation of MAPKs, including p38, JNK and ERK, and their upstream kinases. The application of nsPEFs also elicited elevated phosphorylation of downstream factors including MSK1, Hsp27, ATF2, p90RSK, and c-Jun. In addition, the application of nsPEFs led to the transcriptional activation of immediate early genes in the MAPK pathways. Treatment with inhibitors of the MAPK pathways suppressed nsPEF-induced protein phosphorylation and gene expression downstream of MAPKs, confirming the functional connection between the nsPEF-activated MAPKs and the observed induction of the downstream events. Taken together, these results provide important clues to the action of nsPEFs on human cells and demonstrate a new possibility for the utilization of nsPEFs in the control of various biological phenomena involving activation of the MAPK pathways.