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Role of Glutathione Depletion and Reactive Oxygen Species Generation on Caspase-3 Activation: A Study With the Kinase Inhibitor Staurosporine
Oxidative stress is known to contribute to the progression of apoptosis. Staurosporine is a broad-spectrum inducer of apoptosis, but its mechanism of action is not well understood. The goal of the present work was to elucidate the role of glutathione and reactive oxygen species (ROS) in the executio...
Autores principales: | , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Frontiers Media S.A.
2020
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7485172/ https://www.ncbi.nlm.nih.gov/pubmed/32982774 http://dx.doi.org/10.3389/fphys.2020.00998 |
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author | Musaogullari, Aysenur Mandato, Alysia Chai, Yuh-Cherng |
author_facet | Musaogullari, Aysenur Mandato, Alysia Chai, Yuh-Cherng |
author_sort | Musaogullari, Aysenur |
collection | PubMed |
description | Oxidative stress is known to contribute to the progression of apoptosis. Staurosporine is a broad-spectrum inducer of apoptosis, but its mechanism of action is not well understood. The goal of the present work was to elucidate the role of glutathione and reactive oxygen species (ROS) in the execution of staurosporine-induced apoptosis. HeLa cells were treated with staurosporine at 1 μM for up to 4 h. The concentration of glutathione, generation of ROS, and activation of caspase-3 were measured. The introduction of staurosporine significantly decreased the concentration of cellular glutathione and increased the presence of ROS after 3 h. These findings were concurrent with the activation of caspase-3. Interestingly, pre-treatment of cells with N-acetylcysteine, a precursor of glutathione, and a thiol antioxidant failed to block the depletion of glutathione, generation of ROS, and activation of caspase-3. Collectively, these results suggest that the cellular redox status may be one of the critical factors of the apoptotic pathway leading to caspase-3 activation by staurosporine. |
format | Online Article Text |
id | pubmed-7485172 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-74851722020-09-24 Role of Glutathione Depletion and Reactive Oxygen Species Generation on Caspase-3 Activation: A Study With the Kinase Inhibitor Staurosporine Musaogullari, Aysenur Mandato, Alysia Chai, Yuh-Cherng Front Physiol Physiology Oxidative stress is known to contribute to the progression of apoptosis. Staurosporine is a broad-spectrum inducer of apoptosis, but its mechanism of action is not well understood. The goal of the present work was to elucidate the role of glutathione and reactive oxygen species (ROS) in the execution of staurosporine-induced apoptosis. HeLa cells were treated with staurosporine at 1 μM for up to 4 h. The concentration of glutathione, generation of ROS, and activation of caspase-3 were measured. The introduction of staurosporine significantly decreased the concentration of cellular glutathione and increased the presence of ROS after 3 h. These findings were concurrent with the activation of caspase-3. Interestingly, pre-treatment of cells with N-acetylcysteine, a precursor of glutathione, and a thiol antioxidant failed to block the depletion of glutathione, generation of ROS, and activation of caspase-3. Collectively, these results suggest that the cellular redox status may be one of the critical factors of the apoptotic pathway leading to caspase-3 activation by staurosporine. Frontiers Media S.A. 2020-08-28 /pmc/articles/PMC7485172/ /pubmed/32982774 http://dx.doi.org/10.3389/fphys.2020.00998 Text en Copyright © 2020 Musaogullari, Mandato and Chai. http://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 | Physiology Musaogullari, Aysenur Mandato, Alysia Chai, Yuh-Cherng Role of Glutathione Depletion and Reactive Oxygen Species Generation on Caspase-3 Activation: A Study With the Kinase Inhibitor Staurosporine |
title | Role of Glutathione Depletion and Reactive Oxygen Species Generation on Caspase-3 Activation: A Study With the Kinase Inhibitor Staurosporine |
title_full | Role of Glutathione Depletion and Reactive Oxygen Species Generation on Caspase-3 Activation: A Study With the Kinase Inhibitor Staurosporine |
title_fullStr | Role of Glutathione Depletion and Reactive Oxygen Species Generation on Caspase-3 Activation: A Study With the Kinase Inhibitor Staurosporine |
title_full_unstemmed | Role of Glutathione Depletion and Reactive Oxygen Species Generation on Caspase-3 Activation: A Study With the Kinase Inhibitor Staurosporine |
title_short | Role of Glutathione Depletion and Reactive Oxygen Species Generation on Caspase-3 Activation: A Study With the Kinase Inhibitor Staurosporine |
title_sort | role of glutathione depletion and reactive oxygen species generation on caspase-3 activation: a study with the kinase inhibitor staurosporine |
topic | Physiology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7485172/ https://www.ncbi.nlm.nih.gov/pubmed/32982774 http://dx.doi.org/10.3389/fphys.2020.00998 |
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