Alternating magnetic fields drive stimulation of gene expression via generation of reactive oxygen species

Autor: Jordan W. Mundell, Matthew I. Brier, Everest Orloff, Sarah A. Stanley, Jonathan S. Dordick
Jazyk: angličtina
Rok vydání: 2024
Předmět:
Zdroj: iScience, Vol 27, Iss 3, Pp 109186- (2024)
Druh dokumentu: article
ISSN: 2589-0042
DOI: 10.1016/j.isci.2024.109186
Popis: Summary: Magnetogenetics represents a method for remote control of cellular function. Previous work suggests that generation of reactive oxygen species (ROS) initiates downstream signaling. Herein, a chemical biology approach was used to elucidate further the mechanism of radio frequency-alternating magnetic field (RF-AMF) stimulation of a TRPV1-ferritin magnetogenetics platform that leads to Ca2+ flux. RF-AMF stimulation of HEK293T cells expressing TRPV1-ferritin resulted in ∼30% and ∼140% increase in intra- and extracellular ROS levels, respectively. Mutations to specific cysteine residues in TRPV1 responsible for ROS sensitivity eliminated RF-AMF driven Ca2+-dependent transcription of secreted embryonic alkaline phosphatase (SEAP). Using a non-tethered (to TRPV1) ferritin also eliminated RF-AMF driven SEAP production, and using specific inhibitors, ROS-activated TRPV1 signaling involves protein kinase C, NADPH oxidase, and the endoplasmic reticulum. These results suggest ferritin-dependent ROS activation of TRPV1 plays a key role in the initiation of magnetogenetics, and provides relevance for potential applications in medicine and biotechnology.
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