Exposure of living organisms to short electric pulses is widely utilized in the life sciences, for example, for DNA transfection. Recent advances in electrical engineering have enabled the production of extremely short electric pulses in the range of nanoseconds, namely, nanosecond pulsed electric fields (nsPEFs). nsPEFs are increasingly recognized as a novel means for cancer therapy, because of their ability to induce cell death. Recent studies have demonstrated that nsPEFs act as cellular stress and activate two independent signaling pathways that involve phosphorylation of translation initiation factors and lead to suppression of general protein synthesis. eIF2α phosphorylation is one of the key reactions in stress-induced translational suppression and is rapidly induced by nsPEFs. Concomitantly, PERK and GCN2, both of which are stress-responsive protein kinases, are activated in nsPEF-exposed cells. Furthermore, nsPEFs cause a reduction in 4E-BP1 phosphorylation, which is controlled by mTORC1 and constitutes an alternative mechanism for translational suppression, independent of eIF2α phosphorylation. In accordance with elevated eIF2α phosphorylation and decreased 4E-BP1 phosphorylation, general protein synthesis is acutely suppressed after nsPEF exposure. These findings demonstrate that nsPEFs induce two independent signaling pathways for translational suppression, further highlighting a unique feature of nsPEFs as a novel means for life sciences.
Part of the book: Protein Phosphorylation