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Histone deacetylase inhibitors prevent H(2)O(2) from inducing stress granule formation
Reactive Oxygen Species (ROS) are generated as by-products of aerobic metabolism. The production of ROS increases during xenobiotic stress and under multiple pathological conditions. Although ROS are considered harmful historically, mounting evidence recently indicates a signaling function of ROS, p...
Autores principales: | , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Elsevier
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8320627/ https://www.ncbi.nlm.nih.gov/pubmed/34345843 http://dx.doi.org/10.1016/j.crtox.2020.10.004 |
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author | Feng, Siyuan Daw, Jennifer Nichole Chen, Qin M. |
author_facet | Feng, Siyuan Daw, Jennifer Nichole Chen, Qin M. |
author_sort | Feng, Siyuan |
collection | PubMed |
description | Reactive Oxygen Species (ROS) are generated as by-products of aerobic metabolism. The production of ROS increases during xenobiotic stress and under multiple pathological conditions. Although ROS are considered harmful historically, mounting evidence recently indicates a signaling function of ROS, preceding to and regulating transcriptional or post-transcriptional events, contributing to cell death or cell survival and adaptation. Among the cellular defense mechanisms activated by ROS is formation of stress granules (SGs). The stalled translational apparatus, together with mRNA, aggregates into microscopically detectable and molecularly dynamic granules. We found that with H(2)O(2), the dose most potent for inducing SGs in HeLa cells is 400–600 μM. With 200 μM H(2)O(2), 2 h treatment induced the highest percentage of cells containing SGs. Whether ROS signaling pathways regulate the formation of SGs was tested using pharmacological inhibitors. We probed the potential role of PI3K, MAPKs, PKC or histone deacetylation in SG formation. Using deferoxamine as a positive control, we found a lack of inhibitory effect of wortmannin, LY-294002, JNK-I, SB-202190, PD-98059, or H89 when the percentage of cells containing SGs was counted. About 35% inhibition was observed with HDAC6 inhibitor Tubastatin A, whereas general HDAC inhibitor Trichostatin A provided a complete inhibition of SG formation. Our data point to the need of investigating the role of HDACs in SG formation during oxidative stress. |
format | Online Article Text |
id | pubmed-8320627 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | Elsevier |
record_format | MEDLINE/PubMed |
spelling | pubmed-83206272021-08-02 Histone deacetylase inhibitors prevent H(2)O(2) from inducing stress granule formation Feng, Siyuan Daw, Jennifer Nichole Chen, Qin M. Curr Res Toxicol Article Reactive Oxygen Species (ROS) are generated as by-products of aerobic metabolism. The production of ROS increases during xenobiotic stress and under multiple pathological conditions. Although ROS are considered harmful historically, mounting evidence recently indicates a signaling function of ROS, preceding to and regulating transcriptional or post-transcriptional events, contributing to cell death or cell survival and adaptation. Among the cellular defense mechanisms activated by ROS is formation of stress granules (SGs). The stalled translational apparatus, together with mRNA, aggregates into microscopically detectable and molecularly dynamic granules. We found that with H(2)O(2), the dose most potent for inducing SGs in HeLa cells is 400–600 μM. With 200 μM H(2)O(2), 2 h treatment induced the highest percentage of cells containing SGs. Whether ROS signaling pathways regulate the formation of SGs was tested using pharmacological inhibitors. We probed the potential role of PI3K, MAPKs, PKC or histone deacetylation in SG formation. Using deferoxamine as a positive control, we found a lack of inhibitory effect of wortmannin, LY-294002, JNK-I, SB-202190, PD-98059, or H89 when the percentage of cells containing SGs was counted. About 35% inhibition was observed with HDAC6 inhibitor Tubastatin A, whereas general HDAC inhibitor Trichostatin A provided a complete inhibition of SG formation. Our data point to the need of investigating the role of HDACs in SG formation during oxidative stress. Elsevier 2020-10-31 /pmc/articles/PMC8320627/ /pubmed/34345843 http://dx.doi.org/10.1016/j.crtox.2020.10.004 Text en © 2020 The Authors https://creativecommons.org/licenses/by-nc-nd/4.0/This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/). |
spellingShingle | Article Feng, Siyuan Daw, Jennifer Nichole Chen, Qin M. Histone deacetylase inhibitors prevent H(2)O(2) from inducing stress granule formation |
title | Histone deacetylase inhibitors prevent H(2)O(2) from inducing stress granule formation |
title_full | Histone deacetylase inhibitors prevent H(2)O(2) from inducing stress granule formation |
title_fullStr | Histone deacetylase inhibitors prevent H(2)O(2) from inducing stress granule formation |
title_full_unstemmed | Histone deacetylase inhibitors prevent H(2)O(2) from inducing stress granule formation |
title_short | Histone deacetylase inhibitors prevent H(2)O(2) from inducing stress granule formation |
title_sort | histone deacetylase inhibitors prevent h(2)o(2) from inducing stress granule formation |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8320627/ https://www.ncbi.nlm.nih.gov/pubmed/34345843 http://dx.doi.org/10.1016/j.crtox.2020.10.004 |
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