Cell stress responses to pulsed electric fields

Abstract

Cells are often exposed to unfavorable conditions and stimuli, which are collectively referred to as stress. To adapt to stress, cells induce a set of reactions, called stress responses, that lead to suppression of translation initiation. Protein synthesis requires considerable amounts of energy and amino acids, and hence stressinduced translational suppression preserves cellular resources and serves as a mechanism for survival. This chapter is aimed at providing an overview of the stress responses induced by pulsed electric fields (PEFs). PEFs are utilized in a broad range of the life sciences, owing to their action on the cell membrane. Nanosecond PEFs (nsPEFs) generate small membrane pores that permeate small molecules, such as ions, and longer PEFs yield larger membrane pores suited for DNA transfection and tumor chemotherapy. Irrespective of the pulse width, PEFs are essentially deleterious to cellular homeostasis, because they compromise the membrane integrity and perturb the balance between intra- and extracellular molecules across the cell membrane. Recently, nsPEFs have been shown to induce stress responses in human and mouse cells. nsPEFs elicit stress-responsive signal transduction that comprises two protein kinases, namely, PERK and GCN2, and their substrate eIF2a, leading to translational suppression by eIF2a phosphorylation. nsPEFs affect another signal transduction that controls translation initiation by mTORC1-mediated 4E-BP1 phosphorylation. Collectively, accumulating evidence supports the concept of PEF-induced stress responses that appear to have profound effects on cellular functions such as gene expression and cell death induction.