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N-acetylcysteine Provides Cytoprotection in Murine Oligodendrocytes through Heme Oxygenase-1 Activity

Oligodendrocytic injury by oxidative stress can lead to demyelination, contributing to neurodegeneration. We investigated the mechanisms by which an antioxidant, N-acetylcysteine (NAC), reduces oxidative stress in murine oligodendrocytes. We used normal 158N and mutant 158JP cells with endogenously...

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Autores principales: Zhou, Jie, Terluk, Marcia R., Basso, Lisa, Mishra, Usha R., Orchard, Paul J., Cloyd, James C., Schröder, Henning, Kartha, Reena V.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7460204/
https://www.ncbi.nlm.nih.gov/pubmed/32717964
http://dx.doi.org/10.3390/biomedicines8080240
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author Zhou, Jie
Terluk, Marcia R.
Basso, Lisa
Mishra, Usha R.
Orchard, Paul J.
Cloyd, James C.
Schröder, Henning
Kartha, Reena V.
author_facet Zhou, Jie
Terluk, Marcia R.
Basso, Lisa
Mishra, Usha R.
Orchard, Paul J.
Cloyd, James C.
Schröder, Henning
Kartha, Reena V.
author_sort Zhou, Jie
collection PubMed
description Oligodendrocytic injury by oxidative stress can lead to demyelination, contributing to neurodegeneration. We investigated the mechanisms by which an antioxidant, N-acetylcysteine (NAC), reduces oxidative stress in murine oligodendrocytes. We used normal 158N and mutant 158JP cells with endogenously high reactive oxygen species (ROS) levels. Oxidative stress was induced in 158N cells using hydrogen peroxide (H(2)O(2), 500 μM), and both cells were treated with NAC (50 µM to 500 µM). ROS production, total glutathione (GSH) and cell survival were measured 24 h after treatment. In normal cells, H(2)O(2) treatment resulted in a ~5.5-fold increase in ROS and ~50% cell death. These deleterious effects of oxidative stress were attenuated by NAC, resulting in improved cell survival. Similarly, NAC treatment resulted in decreased ROS levels in 158JP cells. Characterization of mechanisms underlying cytoprotection in both cell lines revealed an increase in GSH levels by NAC, which was partially blocked by an inhibitor of GSH synthesis. Interestingly, we observed heme oxygenase-1 (HO-1), a cytoprotective enzyme, play a critical role in cytoprotection. Inhibition of HO-1 activity abolished the cytoprotective effect of NAC with a corresponding decrease in total antioxidant capacity. Our results indicate that NAC promotes oligodendrocyte survival in oxidative stress-related conditions through multiple pathways.
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spelling pubmed-74602042020-09-02 N-acetylcysteine Provides Cytoprotection in Murine Oligodendrocytes through Heme Oxygenase-1 Activity Zhou, Jie Terluk, Marcia R. Basso, Lisa Mishra, Usha R. Orchard, Paul J. Cloyd, James C. Schröder, Henning Kartha, Reena V. Biomedicines Article Oligodendrocytic injury by oxidative stress can lead to demyelination, contributing to neurodegeneration. We investigated the mechanisms by which an antioxidant, N-acetylcysteine (NAC), reduces oxidative stress in murine oligodendrocytes. We used normal 158N and mutant 158JP cells with endogenously high reactive oxygen species (ROS) levels. Oxidative stress was induced in 158N cells using hydrogen peroxide (H(2)O(2), 500 μM), and both cells were treated with NAC (50 µM to 500 µM). ROS production, total glutathione (GSH) and cell survival were measured 24 h after treatment. In normal cells, H(2)O(2) treatment resulted in a ~5.5-fold increase in ROS and ~50% cell death. These deleterious effects of oxidative stress were attenuated by NAC, resulting in improved cell survival. Similarly, NAC treatment resulted in decreased ROS levels in 158JP cells. Characterization of mechanisms underlying cytoprotection in both cell lines revealed an increase in GSH levels by NAC, which was partially blocked by an inhibitor of GSH synthesis. Interestingly, we observed heme oxygenase-1 (HO-1), a cytoprotective enzyme, play a critical role in cytoprotection. Inhibition of HO-1 activity abolished the cytoprotective effect of NAC with a corresponding decrease in total antioxidant capacity. Our results indicate that NAC promotes oligodendrocyte survival in oxidative stress-related conditions through multiple pathways. MDPI 2020-07-23 /pmc/articles/PMC7460204/ /pubmed/32717964 http://dx.doi.org/10.3390/biomedicines8080240 Text en © 2020 by the authors. 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 (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Zhou, Jie
Terluk, Marcia R.
Basso, Lisa
Mishra, Usha R.
Orchard, Paul J.
Cloyd, James C.
Schröder, Henning
Kartha, Reena V.
N-acetylcysteine Provides Cytoprotection in Murine Oligodendrocytes through Heme Oxygenase-1 Activity
title N-acetylcysteine Provides Cytoprotection in Murine Oligodendrocytes through Heme Oxygenase-1 Activity
title_full N-acetylcysteine Provides Cytoprotection in Murine Oligodendrocytes through Heme Oxygenase-1 Activity
title_fullStr N-acetylcysteine Provides Cytoprotection in Murine Oligodendrocytes through Heme Oxygenase-1 Activity
title_full_unstemmed N-acetylcysteine Provides Cytoprotection in Murine Oligodendrocytes through Heme Oxygenase-1 Activity
title_short N-acetylcysteine Provides Cytoprotection in Murine Oligodendrocytes through Heme Oxygenase-1 Activity
title_sort n-acetylcysteine provides cytoprotection in murine oligodendrocytes through heme oxygenase-1 activity
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7460204/
https://www.ncbi.nlm.nih.gov/pubmed/32717964
http://dx.doi.org/10.3390/biomedicines8080240
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