Cargando…

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...

Descripción completa

Detalles Bibliográficos
Autores principales: Musaogullari, Aysenur, Mandato, Alysia, Chai, Yuh-Cherng
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2020
Materias:
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
_version_ 1783581102674280448
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
work_keys_str_mv AT musaogullariaysenur roleofglutathionedepletionandreactiveoxygenspeciesgenerationoncaspase3activationastudywiththekinaseinhibitorstaurosporine
AT mandatoalysia roleofglutathionedepletionandreactiveoxygenspeciesgenerationoncaspase3activationastudywiththekinaseinhibitorstaurosporine
AT chaiyuhcherng roleofglutathionedepletionandreactiveoxygenspeciesgenerationoncaspase3activationastudywiththekinaseinhibitorstaurosporine