Non-ionizing radiofrequency field induces unfolded protein response (UPR) in endoplasmic reticulum of mouse neuronal cells

Abstract

ObjectiveTo examine whether exposure of mouse neuronal cells to radiofrequency fields used in mobile communication devices can induce stress in endoplasmic reticulum (ER) and activate unfolded protein response (UPR). MethodsHT22 mouse hippocampus neuronal cells were exposed to continuous wave 900 ​MHz radiofrequency fields (RF) at 120 ​μW/cm2 power intensity for 4 ​h/d for 5 consecutive days. The positive control cells were irradiated with 4 ​Gy of 60Co γ-rays at a dose rate of 0.5 ​Gy/min (GR). Twenty-four hours after the last exposure, cells were collected, and the expressions of sensor transmembrane proteins were detected using Western blot analysis. ResultsThe expression levels of Ire1, PERK, p-IRE1 and p-PERK, GRP78 and CHOP proteins were detected. There were no statistically significant differences in the expression levels of IRE1 and PERK proteins in control (CT), sham(SH)-, RF- and GR-exposed cells (P ​< ​0.05). The phosphorylated protein levels of p-IRE1 and p-PERK were significantly increased in cells exposed to RF and GR (P ​< ​0.05). The expression levels of GRP78 and CHOP were significantly increased in RF- and GR-exposed cells compared to CT and SH-exposed cells (P ​< ​0.05). Cells treated with 1 ​μg/ml TM for 24 ​h showed significantly increased expression levels of GRP78 and CHOP proteins compared to controls (P ​< ​0.05). In the presence of 2 ​mmol/L PBA, TM-induced increased levels of GRP78 and CHOP proteins were reduced (P ​< ​0.05). ConclusionsThe exposure of non-ionizing 900 ​MHz RF was able to cause stress in HT22 mouse neuronal cells and activated UPR in ER. Since UPR plays an important role in both cell survival (when UPR is mitigated) and apoptosis/death (under unresolvable stress conditions), further studies are required to determine the fate of the cells exposed to RF.