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

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

Biomedicines (2020-07-29)
Jie Zhou, Marcia R Terluk, Lisa Basso, Usha R Mishra, Paul J Orchard, James C Cloyd, Henning Schröder, Reena V Kartha
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.

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Sigma-Aldrich
Amyloid Protein Non-Aβ Component, ≥80% (HPLC)