N-acetylcysteine provides cytoprotection in murine oligodendrocytes through heme oxygenase-1 activity

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Abstract

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 (H2O2, 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, H2O2 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.

Original languageEnglish (US)
Article number240
JournalBiomedicines
Volume8
Issue number7
DOIs
StatePublished - Jul 2020

Bibliographical note

Funding Information:
Funding: University of Minnesota Academic Health Center Faculty Development Grant and Grant-in-Aid of Research, Artistry, and Scholarship grant offered through the Office of the Vice President for Research, University of Minnesota.

Funding Information:
Acknowledgments: The authors acknowledge funding from the University of Minnesota. The authors also thank S.M. Ghandour (INSERM, France) for the 158N and 158JP cell lines.

Funding Information:
University of Minnesota Academic Health Center Faculty Development Grant and Grant-in-Aid of Research, Artistry, and Scholarship grant offered through the Office of the Vice President for Research, University of Minnesota. The authors acknowledge funding from the University of Minnesota. The authors also thank S.M. Ghandour (INSERM, France) for the 158N and 158JP cell lines.

Publisher Copyright:
© 2020 by the authors.

Keywords

  • Antioxidant
  • Glutathione (GSH)
  • Heme oxygenase-1 (HO-1)
  • N-acetylcysteine
  • Oligodendrocytes
  • Oxidative stress

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