Cargando…
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...
Autores principales: | , , , , , |
---|---|
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 |
_version_ | 1783361995049795584 |
---|---|
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. |
format | Online Article Text |
id | pubmed-6178849 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
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 |
work_keys_str_mv | AT licong activationofglutathioneperoxidase4asanovelantiinflammatorystrategy AT dengxiaobing activationofglutathioneperoxidase4asanovelantiinflammatorystrategy AT xiexiaowen activationofglutathioneperoxidase4asanovelantiinflammatorystrategy AT liuying activationofglutathioneperoxidase4asanovelantiinflammatorystrategy AT friedmannangelijosepedro activationofglutathioneperoxidase4asanovelantiinflammatorystrategy AT lailuhua activationofglutathioneperoxidase4asanovelantiinflammatorystrategy |