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Nogo-A aggravates oxidative damage in oligodendrocytes

Nogo-A is considered one of the most important inhibitors of myelin-associated axonal regeneration in the central nervous system. It is mainly expressed by oligodendrocytes. Although previous studies have found regulatory roles for Nogo-A in neurite outgrowth inhibition, neuronal homeostasis, precur...

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Autores principales: Wang, Yang-Yang, Han, Na, Hong, Dao-Jun, Zhang, Jun
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Wolters Kluwer - Medknow 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7818863/
https://www.ncbi.nlm.nih.gov/pubmed/32788474
http://dx.doi.org/10.4103/1673-5374.286979
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author Wang, Yang-Yang
Han, Na
Hong, Dao-Jun
Zhang, Jun
author_facet Wang, Yang-Yang
Han, Na
Hong, Dao-Jun
Zhang, Jun
author_sort Wang, Yang-Yang
collection PubMed
description Nogo-A is considered one of the most important inhibitors of myelin-associated axonal regeneration in the central nervous system. It is mainly expressed by oligodendrocytes. Although previous studies have found regulatory roles for Nogo-A in neurite outgrowth inhibition, neuronal homeostasis, precursor migration, plasticity, and neurodegeneration, its functions in the process of oxidative injury are largely uncharacterized. In this study, oligodendrocytes were extracted from the cerebral cortex of newborn Sprague-Dawley rats. We used hydrogen peroxide (H(2)O(2)) to induce an in vitro oligodendrocyte oxidative damage model and found that endogenously expressed Nogo-A is significantly upregulated in oligodendrocytes. After recombinant virus Ad-ZsGreen-rat Nogo-A infection of oligodendrocytes, Nogo-A expression was increased, and the infected oligodendrocytes were more susceptible to acute oxidative insults and exhibited a markedly elevated rate of cell death. Furthermore, knockdown of Nogo-A expression in oligodendrocytes by Ad-ZsGreen-shRNA-Nogo-A almost completely protected against oxidative stress induced by exogenous H(2)O(2). Intervention with a Nogo-66 antibody, a LINGO1 blocker, or Y27632, an inhibitor in the Nogo-66-NgR/p75/LINGO-1-RhoA-ROCK pathway, did not affect the death of oligodendrocytes. Ad-ZsGreen-shRNA-Nogo-A also increased the levels of phosphorylated extracellular signal-regulated kinase 1/2 and inhibited BCL2 expression in oligodendrocytes. In conclusion, Nogo-A aggravated reactive oxygen species damage in oligodendrocytes, and phosphorylated extracellular signal-regulated kinase 1/2 and BCL2 might be involved in this process. This study was approved by the Ethics Committee of Peking University People’s Hospital, China (approval No. 2018PHC081) on December 18, 2018.
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spelling pubmed-78188632021-01-22 Nogo-A aggravates oxidative damage in oligodendrocytes Wang, Yang-Yang Han, Na Hong, Dao-Jun Zhang, Jun Neural Regen Res Research Article Nogo-A is considered one of the most important inhibitors of myelin-associated axonal regeneration in the central nervous system. It is mainly expressed by oligodendrocytes. Although previous studies have found regulatory roles for Nogo-A in neurite outgrowth inhibition, neuronal homeostasis, precursor migration, plasticity, and neurodegeneration, its functions in the process of oxidative injury are largely uncharacterized. In this study, oligodendrocytes were extracted from the cerebral cortex of newborn Sprague-Dawley rats. We used hydrogen peroxide (H(2)O(2)) to induce an in vitro oligodendrocyte oxidative damage model and found that endogenously expressed Nogo-A is significantly upregulated in oligodendrocytes. After recombinant virus Ad-ZsGreen-rat Nogo-A infection of oligodendrocytes, Nogo-A expression was increased, and the infected oligodendrocytes were more susceptible to acute oxidative insults and exhibited a markedly elevated rate of cell death. Furthermore, knockdown of Nogo-A expression in oligodendrocytes by Ad-ZsGreen-shRNA-Nogo-A almost completely protected against oxidative stress induced by exogenous H(2)O(2). Intervention with a Nogo-66 antibody, a LINGO1 blocker, or Y27632, an inhibitor in the Nogo-66-NgR/p75/LINGO-1-RhoA-ROCK pathway, did not affect the death of oligodendrocytes. Ad-ZsGreen-shRNA-Nogo-A also increased the levels of phosphorylated extracellular signal-regulated kinase 1/2 and inhibited BCL2 expression in oligodendrocytes. In conclusion, Nogo-A aggravated reactive oxygen species damage in oligodendrocytes, and phosphorylated extracellular signal-regulated kinase 1/2 and BCL2 might be involved in this process. This study was approved by the Ethics Committee of Peking University People’s Hospital, China (approval No. 2018PHC081) on December 18, 2018. Wolters Kluwer - Medknow 2020-08-10 /pmc/articles/PMC7818863/ /pubmed/32788474 http://dx.doi.org/10.4103/1673-5374.286979 Text en Copyright: © 2021 Neural Regeneration Research http://creativecommons.org/licenses/by-nc-sa/4.0 This is an open access journal, and articles are distributed under the terms of the Creative Commons Attribution-NonCommercial-ShareAlike 4.0 License, which allows others to remix, tweak, and build upon the work non-commercially, as long as appropriate credit is given and the new creations are licensed under the identical terms.
spellingShingle Research Article
Wang, Yang-Yang
Han, Na
Hong, Dao-Jun
Zhang, Jun
Nogo-A aggravates oxidative damage in oligodendrocytes
title Nogo-A aggravates oxidative damage in oligodendrocytes
title_full Nogo-A aggravates oxidative damage in oligodendrocytes
title_fullStr Nogo-A aggravates oxidative damage in oligodendrocytes
title_full_unstemmed Nogo-A aggravates oxidative damage in oligodendrocytes
title_short Nogo-A aggravates oxidative damage in oligodendrocytes
title_sort nogo-a aggravates oxidative damage in oligodendrocytes
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7818863/
https://www.ncbi.nlm.nih.gov/pubmed/32788474
http://dx.doi.org/10.4103/1673-5374.286979
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