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Ultrafine Diesel Exhaust Particles Induce Apoptosis of Oligodendrocytes by Increasing Intracellular Reactive Oxygen Species through NADPH Oxidase Activation

Diesel exhaust particles (DEPs) are a main contributor to air pollution. Ultrafine DEPs can cause neurodegenerative diseases by increasing intracellular reactive oxygen species (ROS). Compared with other cells in the brain, oligodendrocytes responsible for myelination are more susceptible to oxidati...

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Autores principales: Kim, Ji Young, Kim, Jin-Hee, Kim, Yong-Dae, Seo, Je Hoon
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9137819/
https://www.ncbi.nlm.nih.gov/pubmed/35624895
http://dx.doi.org/10.3390/antiox11051031
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author Kim, Ji Young
Kim, Jin-Hee
Kim, Yong-Dae
Seo, Je Hoon
author_facet Kim, Ji Young
Kim, Jin-Hee
Kim, Yong-Dae
Seo, Je Hoon
author_sort Kim, Ji Young
collection PubMed
description Diesel exhaust particles (DEPs) are a main contributor to air pollution. Ultrafine DEPs can cause neurodegenerative diseases by increasing intracellular reactive oxygen species (ROS). Compared with other cells in the brain, oligodendrocytes responsible for myelination are more susceptible to oxidative stress. However, the mechanisms underlying ROS generation in oligodendrocytes and the susceptibility of oligodendrocytes to ROS by ultrafine DEPs remain unclear. Herein, we examined the effects of excessive ROS generated by NOX2, an isoform of the NADPH oxidase family, after exposure to ultrafine DEPs (200 μg/mL) on the survival of two types of oligodendrocytes—oligodendrocyte precursor cells (OPCs) and mature oligodendrocytes (mOLs)––isolated from the brain of neonatal rats. In addition, mice were exposed to ultrafine DEP suspension (20 μL, 0.4 mg/mL) via the nasal route for 1 week, after which the expression of NOX2 and cleaved caspase-3 was examined in the white matter of the cerebellum. Exposure to DEPs significantly increased NOX2 expression and ROS generation in OPCs and mOLs. OPCs and mOLs clearly exhibited viability reduction, and a significant change in p53, Bax, Bcl-2, and cleaved caspase-3 expression, after DEP exposure. In contrast, treatment with berberine (BBR), an NOX2 inhibitor, significantly mitigated these effects. In mice exposed to DEP, the presence of NOX2-positive and cleaved caspase-3-positive oligodendrocytes was demonstrated in the cerebellar white matter; NOX2 and cleaved caspase-3 expression in the cerebellum lysates was significantly increased. BBR treatment returned expression of these proteins to control levels. These results demonstrate that the susceptibility of OPCs and mOLs to ultrafine DEPs is, at least in part, caused by excessive ROS produced by NOX2 and the sequential changes in the expression of p53, Bax, Bcl-2, and cleaved caspase-3. Overall, NOX2 inhibitor enhances the survival of two types of oligodendrocytes.
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spelling pubmed-91378192022-05-28 Ultrafine Diesel Exhaust Particles Induce Apoptosis of Oligodendrocytes by Increasing Intracellular Reactive Oxygen Species through NADPH Oxidase Activation Kim, Ji Young Kim, Jin-Hee Kim, Yong-Dae Seo, Je Hoon Antioxidants (Basel) Article Diesel exhaust particles (DEPs) are a main contributor to air pollution. Ultrafine DEPs can cause neurodegenerative diseases by increasing intracellular reactive oxygen species (ROS). Compared with other cells in the brain, oligodendrocytes responsible for myelination are more susceptible to oxidative stress. However, the mechanisms underlying ROS generation in oligodendrocytes and the susceptibility of oligodendrocytes to ROS by ultrafine DEPs remain unclear. Herein, we examined the effects of excessive ROS generated by NOX2, an isoform of the NADPH oxidase family, after exposure to ultrafine DEPs (200 μg/mL) on the survival of two types of oligodendrocytes—oligodendrocyte precursor cells (OPCs) and mature oligodendrocytes (mOLs)––isolated from the brain of neonatal rats. In addition, mice were exposed to ultrafine DEP suspension (20 μL, 0.4 mg/mL) via the nasal route for 1 week, after which the expression of NOX2 and cleaved caspase-3 was examined in the white matter of the cerebellum. Exposure to DEPs significantly increased NOX2 expression and ROS generation in OPCs and mOLs. OPCs and mOLs clearly exhibited viability reduction, and a significant change in p53, Bax, Bcl-2, and cleaved caspase-3 expression, after DEP exposure. In contrast, treatment with berberine (BBR), an NOX2 inhibitor, significantly mitigated these effects. In mice exposed to DEP, the presence of NOX2-positive and cleaved caspase-3-positive oligodendrocytes was demonstrated in the cerebellar white matter; NOX2 and cleaved caspase-3 expression in the cerebellum lysates was significantly increased. BBR treatment returned expression of these proteins to control levels. These results demonstrate that the susceptibility of OPCs and mOLs to ultrafine DEPs is, at least in part, caused by excessive ROS produced by NOX2 and the sequential changes in the expression of p53, Bax, Bcl-2, and cleaved caspase-3. Overall, NOX2 inhibitor enhances the survival of two types of oligodendrocytes. MDPI 2022-05-23 /pmc/articles/PMC9137819/ /pubmed/35624895 http://dx.doi.org/10.3390/antiox11051031 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/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 (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Kim, Ji Young
Kim, Jin-Hee
Kim, Yong-Dae
Seo, Je Hoon
Ultrafine Diesel Exhaust Particles Induce Apoptosis of Oligodendrocytes by Increasing Intracellular Reactive Oxygen Species through NADPH Oxidase Activation
title Ultrafine Diesel Exhaust Particles Induce Apoptosis of Oligodendrocytes by Increasing Intracellular Reactive Oxygen Species through NADPH Oxidase Activation
title_full Ultrafine Diesel Exhaust Particles Induce Apoptosis of Oligodendrocytes by Increasing Intracellular Reactive Oxygen Species through NADPH Oxidase Activation
title_fullStr Ultrafine Diesel Exhaust Particles Induce Apoptosis of Oligodendrocytes by Increasing Intracellular Reactive Oxygen Species through NADPH Oxidase Activation
title_full_unstemmed Ultrafine Diesel Exhaust Particles Induce Apoptosis of Oligodendrocytes by Increasing Intracellular Reactive Oxygen Species through NADPH Oxidase Activation
title_short Ultrafine Diesel Exhaust Particles Induce Apoptosis of Oligodendrocytes by Increasing Intracellular Reactive Oxygen Species through NADPH Oxidase Activation
title_sort ultrafine diesel exhaust particles induce apoptosis of oligodendrocytes by increasing intracellular reactive oxygen species through nadph oxidase activation
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9137819/
https://www.ncbi.nlm.nih.gov/pubmed/35624895
http://dx.doi.org/10.3390/antiox11051031
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