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

Abstract

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.

Cellular Processes Involved in Jurkat Cells Exposed to Nanosecond Pulsed Electric Field

“…After stimulation of cells with nsPEF (100, 10 ns pulses at 150 kV/cm, 1 Hz), the mRNA of the endoplasmic reticulum stress gene did not change. Moreover, the intracellular unfolded protein response (UPR) protein also did not alter [34]. On the contrary, in the present study, these above eight hub genes of Jurkat cells have significant responses to nsPEF stimulation.…”

Nanosecond Pulsed Electric Field Only Transiently Affects the Cellular and Molecular Processes of Leydig Cells

“…Other noteworthy time-related changes included a high overexpression of Fos (FBJ osteosarcoma oncogene), Jun (jun proto-oncogene), and Egr1 (early growth response 1) immediately after nsPEF, both in the sham- and nsPEF-exposed cells. This finding was surprising because previous works strongly associated increased expression of these genes with nsPEF treatment in Jurkat cells and fibroblasts [ 77 , 78 , 79 , 81 ]. Fos , Jun, and Egr1 are well-characterized immediate-early response genes whose transcription is activated within minutes after stimulation with extracellular or intracellular cues (e.g., cytokines, growth factors, shear stress, or UV damage) [ 82 , 83 , 84 ].…”

Rotating magnetic field delays human umbilical vein endothelial cell aging and prolongs the lifespan of Caenorhabditis elegans

“…The response of the endoplasmic reticulum to the magnetic field through the Ca 2+ channel can be used to perceive biophysical information from the magnetic field. The endoplasmic reticulum has been proposed as an enabler of magnetic field intensity-and direction-guided behavior in animals via mechanism that is consistent with an electron eddy hypothesis [27–29]. This hypothesis is based on a requirement for magnetic minerals, such as iron, and proteins containing magnetic substances that act as magnetobiological receptors, which receive and respond to magnetic changes.…”