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Activation of Glutathione Peroxidase 4 as a Novel Anti-inflammatory Strategy

The anti-oxidative enzyme, glutathione peroxidase 4 (GPX4), helps to promote inflammation resolution by eliminating oxidative species produced by the arachidonic acid (AA) metabolic network. Up-regulating its activity has been proposed as a promising strategy for inflammation intervention. In the pr...

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Autores principales: Li, Cong, Deng, Xiaobing, Xie, Xiaowen, Liu, Ying, Friedmann Angeli, José Pedro, Lai, Luhua
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6178849/
https://www.ncbi.nlm.nih.gov/pubmed/30337875
http://dx.doi.org/10.3389/fphar.2018.01120
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author Li, Cong
Deng, Xiaobing
Xie, Xiaowen
Liu, Ying
Friedmann Angeli, José Pedro
Lai, Luhua
author_facet Li, Cong
Deng, Xiaobing
Xie, Xiaowen
Liu, Ying
Friedmann Angeli, José Pedro
Lai, Luhua
author_sort Li, Cong
collection PubMed
description The anti-oxidative enzyme, glutathione peroxidase 4 (GPX4), helps to promote inflammation resolution by eliminating oxidative species produced by the arachidonic acid (AA) metabolic network. Up-regulating its activity has been proposed as a promising strategy for inflammation intervention. In the present study, we aimed to study the effect of GPX4 activator on the AA metabolic network and inflammation related pathways. Using combined computational and experimental screen, we identified a novel compound that can activate the enzyme activity of GPX4 by more than two folds. We further assessed its potential in a series of cellular assays where GPX4 was demonstrated to play a regulatory role. We are able to show that GPX4 activation suppressed inflammatory conditions such as oxidation of AA and NF-κB pathway activation. We further demonstrated that this GPX4 activator can decrease the intracellular ROS level and suppress ferroptosis. Our study suggests that GPX4 activators can be developed as anti-inflammatory or cyto-protective agent in lipid-peroxidation-mediated diseases.
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spelling pubmed-61788492018-10-18 Activation of Glutathione Peroxidase 4 as a Novel Anti-inflammatory Strategy Li, Cong Deng, Xiaobing Xie, Xiaowen Liu, Ying Friedmann Angeli, José Pedro Lai, Luhua Front Pharmacol Pharmacology The anti-oxidative enzyme, glutathione peroxidase 4 (GPX4), helps to promote inflammation resolution by eliminating oxidative species produced by the arachidonic acid (AA) metabolic network. Up-regulating its activity has been proposed as a promising strategy for inflammation intervention. In the present study, we aimed to study the effect of GPX4 activator on the AA metabolic network and inflammation related pathways. Using combined computational and experimental screen, we identified a novel compound that can activate the enzyme activity of GPX4 by more than two folds. We further assessed its potential in a series of cellular assays where GPX4 was demonstrated to play a regulatory role. We are able to show that GPX4 activation suppressed inflammatory conditions such as oxidation of AA and NF-κB pathway activation. We further demonstrated that this GPX4 activator can decrease the intracellular ROS level and suppress ferroptosis. Our study suggests that GPX4 activators can be developed as anti-inflammatory or cyto-protective agent in lipid-peroxidation-mediated diseases. Frontiers Media S.A. 2018-10-03 /pmc/articles/PMC6178849/ /pubmed/30337875 http://dx.doi.org/10.3389/fphar.2018.01120 Text en Copyright © 2018 Li, Deng, Xie, Liu, Friedmann Angeli and Lai. 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 Pharmacology
Li, Cong
Deng, Xiaobing
Xie, Xiaowen
Liu, Ying
Friedmann Angeli, José Pedro
Lai, Luhua
Activation of Glutathione Peroxidase 4 as a Novel Anti-inflammatory Strategy
title Activation of Glutathione Peroxidase 4 as a Novel Anti-inflammatory Strategy
title_full Activation of Glutathione Peroxidase 4 as a Novel Anti-inflammatory Strategy
title_fullStr Activation of Glutathione Peroxidase 4 as a Novel Anti-inflammatory Strategy
title_full_unstemmed Activation of Glutathione Peroxidase 4 as a Novel Anti-inflammatory Strategy
title_short Activation of Glutathione Peroxidase 4 as a Novel Anti-inflammatory Strategy
title_sort activation of glutathione peroxidase 4 as a novel anti-inflammatory strategy
topic Pharmacology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6178849/
https://www.ncbi.nlm.nih.gov/pubmed/30337875
http://dx.doi.org/10.3389/fphar.2018.01120
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