Nanosecond pulsed electric field exposure does not induce the unfolded protein response in adult human dermal fibroblasts

Cell-circuit models have suggested that nanosecond pulsed electric fields (nsPEFs) can disrupt intracellular membranes including endoplasmic reticulum (ER), mitochondria, and/or nucleus thereby inducing intrinsic apoptotic pathways. Therefore, we hypothesized that the unfolded protein response (UPR) would be activated, due to the fluctuations of ionic concentrations, upon poration of the ER membrane. Quantitative real-time polymerase chain reaction was utilized to measure changes in messenger RNA (mRNA) expression of specific ER stress genes in adult human dermal fibroblast (HDFa) cells treated with tunicamycin (TM) (known ER stress inducer) and cells exposed to nsPEFs (100, 10-ns pulses at 150 kV/cm delivered at a repetition rate of 1 Hz). For HDFa cells, results showed time-dependent UPR activation to TM; however, when HDFa cells were exposed to nsPEFs, no significant changes in mRNA expression of ER stress genes, and/or caspase gene were observed. These results indicate that although cell death can be observed under these exposure parameters, it is most likely not initiated through activation of the UPR. Bioelectromagnetics. 2018;39:491-499, 2018. Published 2018. This article is a U.S. Government work and is in the public domain in the USA.