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Lipid Peroxides Mediated Ferroptosis in Electromagnetic Pulse-Induced Hippocampal Neuronal Damage via Inhibition of GSH/GPX4 Axis

Electromagnetic pulse (EMP) radiation was reported to be harmful to hippocampal neurons. However, the mechanism underlying EMP-induced neuronal damage remains unclear. In this paper, for the first time, we attempted to investigate the involvement of ferroptosis in EMP-induced neuronal damage and its...

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Autores principales: Lai, Yunfei, Dong, Ji, Wu, You, Zhao, Li, Wang, Hui, Zhang, Jing, Yao, Binwei, Xu, Xinping, Zou, Yong, Zhao, Haixia, Yue, Hanlin, Song, Yiwei, Wang, Haoyu, Peng, Ruiyun
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9409492/
https://www.ncbi.nlm.nih.gov/pubmed/36012537
http://dx.doi.org/10.3390/ijms23169277
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author Lai, Yunfei
Dong, Ji
Wu, You
Zhao, Li
Wang, Hui
Zhang, Jing
Yao, Binwei
Xu, Xinping
Zou, Yong
Zhao, Haixia
Yue, Hanlin
Song, Yiwei
Wang, Haoyu
Peng, Ruiyun
author_facet Lai, Yunfei
Dong, Ji
Wu, You
Zhao, Li
Wang, Hui
Zhang, Jing
Yao, Binwei
Xu, Xinping
Zou, Yong
Zhao, Haixia
Yue, Hanlin
Song, Yiwei
Wang, Haoyu
Peng, Ruiyun
author_sort Lai, Yunfei
collection PubMed
description Electromagnetic pulse (EMP) radiation was reported to be harmful to hippocampal neurons. However, the mechanism underlying EMP-induced neuronal damage remains unclear. In this paper, for the first time, we attempted to investigate the involvement of ferroptosis in EMP-induced neuronal damage and its underlying mechanism. In vivo studies were conducted with a rat model to examine the association of ferroptosis and EMP-induced hippocampal neuronal damage. Moreover, in vitro studies were conducted with HT22 neurons to investigate the underlying mechanism of EMP-induced neuronal ferroptosis. In vivo results showed that EMP could induce learning and memory impairment of rats, ferroptotic morphological damages to mitochondria, accumulation of malonaldehyde (MDA) and iron, overexpression of prostaglandin-endoperoxide synthase 2 (PTGS2) mRNA, and downregulation of GPX4 protein in rat hippocampus. In vitro results showed that EMP could induce neuronal death, MDA accumulation, iron overload, PTGS2 overexpression, and GPX4 downregulation in HT22 neurons. These adverse effects could be reversed by either lipid peroxides scavenger ferrostatin-1 or overexpression of GPX4. These results suggest that EMP radiation can induce ferroptosis in hippocampal neurons via a vicious cycle of lipid peroxides accumulation and GSH/GPX4 axis downregulation. Lipid peroxides and the GSH/GPX4 axis provide potential effective intervention targets to EMP-induced hippocampal neuronal damage.
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spelling pubmed-94094922022-08-26 Lipid Peroxides Mediated Ferroptosis in Electromagnetic Pulse-Induced Hippocampal Neuronal Damage via Inhibition of GSH/GPX4 Axis Lai, Yunfei Dong, Ji Wu, You Zhao, Li Wang, Hui Zhang, Jing Yao, Binwei Xu, Xinping Zou, Yong Zhao, Haixia Yue, Hanlin Song, Yiwei Wang, Haoyu Peng, Ruiyun Int J Mol Sci Article Electromagnetic pulse (EMP) radiation was reported to be harmful to hippocampal neurons. However, the mechanism underlying EMP-induced neuronal damage remains unclear. In this paper, for the first time, we attempted to investigate the involvement of ferroptosis in EMP-induced neuronal damage and its underlying mechanism. In vivo studies were conducted with a rat model to examine the association of ferroptosis and EMP-induced hippocampal neuronal damage. Moreover, in vitro studies were conducted with HT22 neurons to investigate the underlying mechanism of EMP-induced neuronal ferroptosis. In vivo results showed that EMP could induce learning and memory impairment of rats, ferroptotic morphological damages to mitochondria, accumulation of malonaldehyde (MDA) and iron, overexpression of prostaglandin-endoperoxide synthase 2 (PTGS2) mRNA, and downregulation of GPX4 protein in rat hippocampus. In vitro results showed that EMP could induce neuronal death, MDA accumulation, iron overload, PTGS2 overexpression, and GPX4 downregulation in HT22 neurons. These adverse effects could be reversed by either lipid peroxides scavenger ferrostatin-1 or overexpression of GPX4. These results suggest that EMP radiation can induce ferroptosis in hippocampal neurons via a vicious cycle of lipid peroxides accumulation and GSH/GPX4 axis downregulation. Lipid peroxides and the GSH/GPX4 axis provide potential effective intervention targets to EMP-induced hippocampal neuronal damage. MDPI 2022-08-17 /pmc/articles/PMC9409492/ /pubmed/36012537 http://dx.doi.org/10.3390/ijms23169277 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Lai, Yunfei
Dong, Ji
Wu, You
Zhao, Li
Wang, Hui
Zhang, Jing
Yao, Binwei
Xu, Xinping
Zou, Yong
Zhao, Haixia
Yue, Hanlin
Song, Yiwei
Wang, Haoyu
Peng, Ruiyun
Lipid Peroxides Mediated Ferroptosis in Electromagnetic Pulse-Induced Hippocampal Neuronal Damage via Inhibition of GSH/GPX4 Axis
title Lipid Peroxides Mediated Ferroptosis in Electromagnetic Pulse-Induced Hippocampal Neuronal Damage via Inhibition of GSH/GPX4 Axis
title_full Lipid Peroxides Mediated Ferroptosis in Electromagnetic Pulse-Induced Hippocampal Neuronal Damage via Inhibition of GSH/GPX4 Axis
title_fullStr Lipid Peroxides Mediated Ferroptosis in Electromagnetic Pulse-Induced Hippocampal Neuronal Damage via Inhibition of GSH/GPX4 Axis
title_full_unstemmed Lipid Peroxides Mediated Ferroptosis in Electromagnetic Pulse-Induced Hippocampal Neuronal Damage via Inhibition of GSH/GPX4 Axis
title_short Lipid Peroxides Mediated Ferroptosis in Electromagnetic Pulse-Induced Hippocampal Neuronal Damage via Inhibition of GSH/GPX4 Axis
title_sort lipid peroxides mediated ferroptosis in electromagnetic pulse-induced hippocampal neuronal damage via inhibition of gsh/gpx4 axis
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9409492/
https://www.ncbi.nlm.nih.gov/pubmed/36012537
http://dx.doi.org/10.3390/ijms23169277
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