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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...

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Autores principales: Feng, Siyuan, Daw, Jennifer Nichole, Chen, Qin M.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Elsevier 2020
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.
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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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