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The integrated stress response (ISR) is one of the most important cytoprotective mechanisms and is integrated by phosphorylation of the α subunit of eukaryotic translation initiation factor 2 (eIF2α). Four eIF2α kinases, heme-regulated inhibitor (HRI), double-stranded RNA-dependent protein kinase (PKR), PKR-like endoplasmic reticulum kinase (PERK), and general control nonderepressible 2 (GCN2), are activated in response to several stress conditions. We previously reported that nanosecond pulsed electric fields (nsPEFs) are a potential therapeutic tool for ISR activation. In this study, we examined which eIF2α kinase is activated by nsPEF treatment. To assess the responsible eIF2α kinase, we used previously established eIF2α kinase quadruple knockout (4KO) and single eIF2α kinase-rescued 4KO mouse embryonic fibroblast (MEF) cells. nsPEFs 70 ns in duration with 30 kV/cm electric fields caused eIF2α phosphorylation in wild-type (WT) MEF cells. On the other hand, nsPEF-induced eIF2α phosphorylation was completely abolished in 4KO MEF cells and was recovered by HRI overexpression. CM-H2DCFDA staining showed that nsPEFs generated reactive oxygen species (ROS), which activated HRI. nsPEF-induced eIF2α phosphorylation was blocked by treatment with the ROS scavenger N-acetyl-L-cysteine (NAC). Our results indicate that the eIF2α kinase HRI is responsible for nsPEF-induced ISR activation and is activated by nsPEF-generated ROS.
This article was published in the following journal.
Name: PloS one
Electric fields can be a powerful tool to interact with enzymes or proteins, with an intriguing perspective to allow protein manipulation. Recently, researchers have focused the interest on intracellu...
Nanosecond pulsed electric field technology (also known as Nano-Pulse Stimulation or NPS) is a nonthermal, drug-free, energy-based technology that has demonstrated effects on cellular structures of th...
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Background: The therapy with pulsed electromagnetic fields (PEFs) has been used as a therapeutic modality for at least 40 years. However, their effect in the migraine prophylaxis is unclea...
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The investigators are looking to determine the effects of PEMFs device on cerebral blood flow and cognition in healthy volunteers. Through in vitro tests and in vivo animal studies, the in...
The purpose of this research is to compare two different approaches for treating patients with stress urinary incontinence: neuromuscular re-education, impairment-based exercise and electr...
The measurement of magnetic fields over the head generated by electric currents in the brain. As in any electrical conductor, electric fields in the brain are accompanied by orthogonal magnetic fields. The measurement of these fields provides information about the localization of brain activity which is complementary to that provided by ELECTROENCEPHALOGRAPHY. Magnetoencephalography may be used alone or together with electroencephalography, for measurement of spontaneous or evoked activity, and for research or clinical purposes.
Fields representing the joint interplay of electric and magnetic forces.
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Electrophoresis in which the direction of the electric field is changed periodically. This technique is similar to other electrophoretic methods normally used to separate double-stranded DNA molecules ranging in size up to tens of thousands of base-pairs. However, by alternating the electric field direction one is able to separate DNA molecules up to several million base-pairs in length.
Physical manipulation of animals and humans to induce a behavioral or other psychological reaction. In experimental psychology, the animal is handled to induce a stress situation or to study the effects of "gentling" or "mothering".
Adhd Anorexia Depression Dyslexia Mental Health Psychiatry Schizophrenia Stress Mental health, although not being as obvious as physical health, is very important, causing great unhappiness to those affected, causing add...
Stress is caused by your perception of situations around you and then the reaction of your body to them. The automatic stress response to unexpected events is known as 'fight or flight'. Discovered by Walter Cannon in 1932, it is the release of h...