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Up-regulation of GluN2A-containing NMDA receptor protects cultured cortical neuron cells from oxidative stress

Neuronal excitotoxicity induced by spreading depolarization occurs during multiple brain diseases. The subsequent extensive releasing of neuronal transmitter glutamate results in over activation of the ionic glutamate receptors and then triggers neuronal cell death. The N-methyl-D-aspartate (NMDA) r...

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Autores principales: Zhu, Jia, Xu, Shilian, Li, Shengpei, Yang, Xueling, Yu, Xianhui, Zhang, Xiaomin
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Elsevier 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6275848/
https://www.ncbi.nlm.nih.gov/pubmed/30555952
http://dx.doi.org/10.1016/j.heliyon.2018.e00976
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author Zhu, Jia
Xu, Shilian
Li, Shengpei
Yang, Xueling
Yu, Xianhui
Zhang, Xiaomin
author_facet Zhu, Jia
Xu, Shilian
Li, Shengpei
Yang, Xueling
Yu, Xianhui
Zhang, Xiaomin
author_sort Zhu, Jia
collection PubMed
description Neuronal excitotoxicity induced by spreading depolarization occurs during multiple brain diseases. The subsequent extensive releasing of neuronal transmitter glutamate results in over activation of the ionic glutamate receptors and then triggers neuronal cell death. The N-methyl-D-aspartate (NMDA) receptor is one major type of excitatory ionic glutamate receptors in the central nervous system, and it exerts vital functions on the membrane of neurons. Distinct subtypes of the NMDA receptor play different roles and their expression was dynamically regulated according to both physiological and pathological stimulations. During neuronal excitotoxicity the expression of the GluN2A-containing NMDA receptor is specifically up-regulated, and as a result, the ratio of GluN2A- versus GluN2B-containing NMDA receptors is altered. However the physiological significance of this phenomenon is still not clear. In this research, we specifically inhibited the increase of the GluN2A-containing NMDA receptor by a peptide without affecting the basic expression of both GluN2A- and GluN2B-containing NMDA receptors, and found that the oxidative stress of neurons was intensified, with increased endogenous reactive oxygen species (ROS), loss of mitochondrial membrane potential, and elevated expressions of Bcl-2-associated X protein (Bax) and apoptosis-inducing factor (AIF). Furthermore, the phosphorylation of Akt and ERK were also inhibited. These results indicated that the dynamic expression of the GluN2A-containing NMDA receptor played crucial roles in protecting neurons from excitotoxicity.
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spelling pubmed-62758482018-12-14 Up-regulation of GluN2A-containing NMDA receptor protects cultured cortical neuron cells from oxidative stress Zhu, Jia Xu, Shilian Li, Shengpei Yang, Xueling Yu, Xianhui Zhang, Xiaomin Heliyon Article Neuronal excitotoxicity induced by spreading depolarization occurs during multiple brain diseases. The subsequent extensive releasing of neuronal transmitter glutamate results in over activation of the ionic glutamate receptors and then triggers neuronal cell death. The N-methyl-D-aspartate (NMDA) receptor is one major type of excitatory ionic glutamate receptors in the central nervous system, and it exerts vital functions on the membrane of neurons. Distinct subtypes of the NMDA receptor play different roles and their expression was dynamically regulated according to both physiological and pathological stimulations. During neuronal excitotoxicity the expression of the GluN2A-containing NMDA receptor is specifically up-regulated, and as a result, the ratio of GluN2A- versus GluN2B-containing NMDA receptors is altered. However the physiological significance of this phenomenon is still not clear. In this research, we specifically inhibited the increase of the GluN2A-containing NMDA receptor by a peptide without affecting the basic expression of both GluN2A- and GluN2B-containing NMDA receptors, and found that the oxidative stress of neurons was intensified, with increased endogenous reactive oxygen species (ROS), loss of mitochondrial membrane potential, and elevated expressions of Bcl-2-associated X protein (Bax) and apoptosis-inducing factor (AIF). Furthermore, the phosphorylation of Akt and ERK were also inhibited. These results indicated that the dynamic expression of the GluN2A-containing NMDA receptor played crucial roles in protecting neurons from excitotoxicity. Elsevier 2018-11-29 /pmc/articles/PMC6275848/ /pubmed/30555952 http://dx.doi.org/10.1016/j.heliyon.2018.e00976 Text en © 2018 The Authors http://creativecommons.org/licenses/by-nc-nd/4.0/ This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
spellingShingle Article
Zhu, Jia
Xu, Shilian
Li, Shengpei
Yang, Xueling
Yu, Xianhui
Zhang, Xiaomin
Up-regulation of GluN2A-containing NMDA receptor protects cultured cortical neuron cells from oxidative stress
title Up-regulation of GluN2A-containing NMDA receptor protects cultured cortical neuron cells from oxidative stress
title_full Up-regulation of GluN2A-containing NMDA receptor protects cultured cortical neuron cells from oxidative stress
title_fullStr Up-regulation of GluN2A-containing NMDA receptor protects cultured cortical neuron cells from oxidative stress
title_full_unstemmed Up-regulation of GluN2A-containing NMDA receptor protects cultured cortical neuron cells from oxidative stress
title_short Up-regulation of GluN2A-containing NMDA receptor protects cultured cortical neuron cells from oxidative stress
title_sort up-regulation of glun2a-containing nmda receptor protects cultured cortical neuron cells from oxidative stress
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6275848/
https://www.ncbi.nlm.nih.gov/pubmed/30555952
http://dx.doi.org/10.1016/j.heliyon.2018.e00976
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