Biomaterial Database

Lipid Peroxides Mediated Ferroptosis in Electromagnetic Pulse-Induced Hippocampal Neuronal Damage via Inhibition of GSH/GPX4 Axis. 2022

Yunfei Lai, and Ji Dong, and You Wu, and Li Zhao, and Hui Wang, and Jing Zhang, and Binwei Yao, and Xinping Xu, and Yong Zou, and Haixia Zhao, and Hanlin Yue, and Yiwei Song, and Haoyu Wang, and Ruiyun Peng

Beijing Institute of Radiation Medicine, Beijing 100850, China.

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.

UI	MeSH Term	Description	Entries
D008054	Lipid Peroxides	Peroxides produced in the presence of a free radical by the oxidation of unsaturated fatty acids in the cell in the presence of molecular oxygen. The formation of lipid peroxides results in the destruction of the original lipid leading to the loss of integrity of the membranes. They therefore cause a variety of toxic effects in vivo and their formation is considered a pathological process in biological systems. Their formation can be inhibited by antioxidants, such as vitamin E, structural separation or low oxygen tension.	Fatty Acid Hydroperoxide,Lipid Peroxide,Lipoperoxide,Fatty Acid Hydroperoxides,Lipid Hydroperoxide,Lipoperoxides,Acid Hydroperoxide, Fatty,Acid Hydroperoxides, Fatty,Hydroperoxide, Fatty Acid,Hydroperoxide, Lipid,Hydroperoxides, Fatty Acid,Peroxide, Lipid,Peroxides, Lipid
D009474	Neurons	The basic cellular units of nervous tissue. Each neuron consists of a body, an axon, and dendrites. Their purpose is to receive, conduct, and transmit impulses in the NERVOUS SYSTEM.	Nerve Cells,Cell, Nerve,Cells, Nerve,Nerve Cell,Neuron
D006624	Hippocampus	A curved elevation of GRAY MATTER extending the entire length of the floor of the TEMPORAL HORN of the LATERAL VENTRICLE (see also TEMPORAL LOBE). The hippocampus proper, subiculum, and DENTATE GYRUS constitute the hippocampal formation. Sometimes authors include the ENTORHINAL CORTEX in the hippocampal formation.	Ammon Horn,Cornu Ammonis,Hippocampal Formation,Subiculum,Ammon's Horn,Hippocampus Proper,Ammons Horn,Formation, Hippocampal,Formations, Hippocampal,Hippocampal Formations,Hippocampus Propers,Horn, Ammon,Horn, Ammon's,Proper, Hippocampus,Propers, Hippocampus,Subiculums
D000079403	Ferroptosis	A form of REGULATED CELL DEATH initiated by oxidative perturbations of the intracellular microenvironment that is under constitutive control by glutathione peroxidase 4 and can be inhibited by iron chelators and lipophilic antioxidants.	Oxytosis
D000080662	Phospholipid Hydroperoxide Glutathione Peroxidase	A selenoenzyme that converts GLUTATHIONE plus FATTY ACID HYDROPEROXIDES to GLUTATHIONE DISULFIDE plus hydroxy fatty acids and water.	GPX4 Phospholipid Hydroperoxide Glutathione Peroxidase,Glutathione Peroxidase 4,PH-GPeroxidase,PHGPx Enzyme,Phospholipid Hydroperoxide Glutathione Peroxidase GPX4,Phospholipid-Hydroperoxide Glutathione Peroxidase,Selenium-Dependent Glutathione Peroxidase Type-4,Glutathione Peroxidase, Phospholipid-Hydroperoxide,PH GPeroxidase,Selenium Dependent Glutathione Peroxidase Type 4
D000818	Animals	Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA.	Animal,Metazoa,Animalia
D051381	Rats	The common name for the genus Rattus.	Rattus,Rats, Laboratory,Rats, Norway,Rattus norvegicus,Laboratory Rat,Laboratory Rats,Norway Rat,Norway Rats,Rat,Rat, Laboratory,Rat, Norway,norvegicus, Rattus
D051546	Cyclooxygenase 2	An inducibly-expressed subtype of prostaglandin-endoperoxide synthase. It plays an important role in many cellular processes and INFLAMMATION. It is the target of COX2 INHIBITORS.	COX-2 Prostaglandin Synthase,Cyclo-Oxygenase II,Cyclooxygenase-2,PGHS-2,PTGS2,Prostaglandin H Synthase-2,COX 2 Prostaglandin Synthase,Cyclo Oxygenase II,Prostaglandin H Synthase 2,Prostaglandin Synthase, COX-2,Synthase, COX-2 Prostaglandin
D055590	Electromagnetic Phenomena	Characteristics of ELECTRICITY and magnetism such as charged particles and the properties and behavior of charged particles, and other phenomena related to or associated with electromagnetism.	Electrical Concepts,Electromagnetic Concepts,Electrical Phenomena,Electrical Phenomenon,Electromagnetic Phenomenon,Electromagnetics,Concept, Electrical,Concept, Electromagnetic,Concepts, Electrical,Concepts, Electromagnetic,Electrical Concept,Electromagnetic Concept,Electromagnetic Phenomenas,Phenomena, Electrical,Phenomena, Electromagnetic,Phenomenon, Electrical,Phenomenon, Electromagnetic