EFFECTS ON ENDOPLASMIC RETICULUM STRESS RESPONSE OF APPLYING NANOSECOND PULSED ELECTRIC FIELDS

Recently, pulsed power technology has been applied to biological and medical fields. In particular, nanosecond pulsed electric fields (nsPEFs) have been expected to cause various biological reactions. This study explored to induction of endoplasmic reticulum (ER) stress response by nsPEFs in vivo and in vitro experiments. The ER stress is considered cause of disorders, such as diabetes and obesity. The control of ER stress response by nsPEFs can establish a new prevention and therapy for the disorders. A Blumlien-type pulse forming network (B-PFN) applied 14 ns-width voltage pulses on samples. The phosphorylation of eIF2 alpha (P-eIF2 alpha) was analyzed by western blotting and expression of mRNA related to P-eIF2 alpha were evaluated by RT-PCR analysis. In vivo experiments, skeletal muscles of mice were exposed to the nsPEFs. The amount of Atf3, Atf4, CHOP, and Gadd34 which were ER stress sensor, was evaluated. The nsPEFs application induced the P-eIF2 alpha, but other stress than ER stress response might be included. In vitro experiments adopted cultured cells as HeLa cells, HEK293 cells, and MEF cells. In HeLa cells, the P-eIF2 alpha was confirmed and it depended on the number of applied pulses and the applied electric field. In western blotting for HEK293 and MEF cells, the P-eIF2 alpha might occurred but consistent responses was not confirmed. The sensitivity for the nsPEFs would depend on cell species.