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Evidences of plasma membrane-mediated ROS generation upon ELF exposure in neuroblastoma cells supported by a computational multiscale approach

TitleEvidences of plasma membrane-mediated ROS generation upon ELF exposure in neuroblastoma cells supported by a computational multiscale approach
Publication TypeArticolo su Rivista peer-reviewed
Year of Publication2019
AuthorsMerla, Caterina, Liberti M., Consales Claudia, Denzi A., Apollonio F., Marino Carmela, and Benassi Barbara
JournalBiochimica et Biophysica Acta - Biomembranes
Volume1861
Pagination1446-1457
ISSN00052736
Keywordsanalytic method, article, Cell interaction, cell membrane, cell structure, computational multiscale approach, diphenyliodonium salt, dosimetry, electric field, exposure, extremely low frequency magnetic field, human, human cell, in vitro study, magnetic field, model, neuroblastoma cell, Oxidative stress, priority journal, reactive oxygen metabolite, SH-SY5Y cell line, validation process
Abstract

Background: Molecular mechanisms of interaction between cells and extremely low frequency magnetic fields (ELF-MFs) still represent a matter of scientific debate. In this paper, to identify the possible primary source of oxidative stress induced by ELF-MF in SH-SY5Y human neuroblastoma cells, we estimated the induced electric field and current density at the cell level. Methods: We followed a computational multiscale approach, estimating the local electric field and current density from the whole sample down to the single cell level. The procedure takes into account morphological modeling of SH-SY5Y cells, arranged in different topologies. Experimental validation has been carried out: neuroblastoma cells have been treated with Diphenyleneiodonium (DPI) -an inhibitor of the plasma membrane enzyme NADPH oxidase (Nox)- administered 24 h before exposure to 50 Hz (1 mT) MF. Results: Macroscopic and microscopic dosimetric evaluations suggest that increased current densities are induced at the plasma membrane/extra-cellular medium interface; identifying the plasma membrane as the main site of the ELF-neuroblastoma cell interaction. The in vitro results provide an experimental proof that plasma membrane Nox exerts a key role in the redox imbalance elicited by ELF, as DPI treatment reverts the generation of reactive oxygen species induced by ELF exposure. General significance: Microscopic current densities induced at the plasma membrane are likely to play an active physical role in eliciting ELF effects related to redox imbalance. Multiscale computational dosimetry, supported by an in vitro approach for validation, is proposed as the innovative and rigorous paradigm to unveil mechanisms underlying the complex ELF-MF interactions. © 2019 Elsevier B.V.

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URLhttps://www.scopus.com/inward/record.uri?eid=2-s2.0-85067629319&doi=10.1016%2fj.bbamem.2019.06.005&partnerID=40&md5=e08f3dd78c817df0e1f41503ec29c6ad
DOI10.1016/j.bbamem.2019.06.005
Citation KeyMerla20191446