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Glutathione S-transferases Control astrocyte activation and neuronal health during neuroinflammation

Glutathione S-transferases (GST) are phase II detoxification enzymes of xenobiotic metabolism and readily expressed in the brain. Nevertheless, the current knowledge about their roles in the brain is limited. We have recently discovered that GSTM1 promotes the production of pro-inflammatory mediator...

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Autores principales: Matoba, Ken, Dohi, Eisuke, Choi, Eric Y., Kano, Shin-ichi
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9853189/
https://www.ncbi.nlm.nih.gov/pubmed/36685285
http://dx.doi.org/10.3389/fmolb.2022.1080140
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author Matoba, Ken
Dohi, Eisuke
Choi, Eric Y.
Kano, Shin-ichi
author_facet Matoba, Ken
Dohi, Eisuke
Choi, Eric Y.
Kano, Shin-ichi
author_sort Matoba, Ken
collection PubMed
description Glutathione S-transferases (GST) are phase II detoxification enzymes of xenobiotic metabolism and readily expressed in the brain. Nevertheless, the current knowledge about their roles in the brain is limited. We have recently discovered that GSTM1 promotes the production of pro-inflammatory mediators by astrocytes and enhances microglial activation during acute brain inflammation. Here we report that GSTM1 significantly affects TNF-α-dependent transcriptional program in astrocytes and modulates neuronal activities and stress during brain inflammation. We have found that a reduced expression of GSTM1 in astrocytes downregulates the expression of pro-inflammatory genes while upregulating the expression of genes involved in interferon responses and fatty acid metabolism. Our data also revealed that GSTM1 reduction in astrocytes increased neuronal stress levels, attenuating neuronal activities during LPS-induced brain inflammation. Furthermore, we found that GSTM1 expression increased in the frontal cortex and hippocampus of aging mice. Thus, this study has further advanced our understanding of the role of Glutathione S-transferases in astrocytes during brain inflammation and paved the way for future studies to determine the critical role of GSTM1 in reactive astrocyte responses in inflammation and aging.
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spelling pubmed-98531892023-01-21 Glutathione S-transferases Control astrocyte activation and neuronal health during neuroinflammation Matoba, Ken Dohi, Eisuke Choi, Eric Y. Kano, Shin-ichi Front Mol Biosci Molecular Biosciences Glutathione S-transferases (GST) are phase II detoxification enzymes of xenobiotic metabolism and readily expressed in the brain. Nevertheless, the current knowledge about their roles in the brain is limited. We have recently discovered that GSTM1 promotes the production of pro-inflammatory mediators by astrocytes and enhances microglial activation during acute brain inflammation. Here we report that GSTM1 significantly affects TNF-α-dependent transcriptional program in astrocytes and modulates neuronal activities and stress during brain inflammation. We have found that a reduced expression of GSTM1 in astrocytes downregulates the expression of pro-inflammatory genes while upregulating the expression of genes involved in interferon responses and fatty acid metabolism. Our data also revealed that GSTM1 reduction in astrocytes increased neuronal stress levels, attenuating neuronal activities during LPS-induced brain inflammation. Furthermore, we found that GSTM1 expression increased in the frontal cortex and hippocampus of aging mice. Thus, this study has further advanced our understanding of the role of Glutathione S-transferases in astrocytes during brain inflammation and paved the way for future studies to determine the critical role of GSTM1 in reactive astrocyte responses in inflammation and aging. Frontiers Media S.A. 2023-01-06 /pmc/articles/PMC9853189/ /pubmed/36685285 http://dx.doi.org/10.3389/fmolb.2022.1080140 Text en Copyright © 2023 Matoba, Dohi, Choi and Kano. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Molecular Biosciences
Matoba, Ken
Dohi, Eisuke
Choi, Eric Y.
Kano, Shin-ichi
Glutathione S-transferases Control astrocyte activation and neuronal health during neuroinflammation
title Glutathione S-transferases Control astrocyte activation and neuronal health during neuroinflammation
title_full Glutathione S-transferases Control astrocyte activation and neuronal health during neuroinflammation
title_fullStr Glutathione S-transferases Control astrocyte activation and neuronal health during neuroinflammation
title_full_unstemmed Glutathione S-transferases Control astrocyte activation and neuronal health during neuroinflammation
title_short Glutathione S-transferases Control astrocyte activation and neuronal health during neuroinflammation
title_sort glutathione s-transferases control astrocyte activation and neuronal health during neuroinflammation
topic Molecular Biosciences
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9853189/
https://www.ncbi.nlm.nih.gov/pubmed/36685285
http://dx.doi.org/10.3389/fmolb.2022.1080140
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