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

Please always quote using this URN: urn:nbn:de:bvb:20-opus-195985
  • 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 ofThe 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.show moreshow less

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Metadaten
Author: Cong Li, Xiaobing Deng, Xiaowen Xie, Ying Liu, José Pedro Friedmann Angeli, Luhua Lai
URN:urn:nbn:de:bvb:20-opus-195985
Document Type:Journal article
Faculties:Fakultät für Biologie / Rudolf-Virchow-Zentrum
Language:English
Parent Title (English):Frontiers in Pharmacology
ISSN:1663-9812
Year of Completion:2018
Volume:9
Issue:1120
Source:Frontiers in Pharmacology 2018, 9:1120. doi: 10.3389/fphar.2018.01120
DOI:https://doi.org/10.3389/fphar.2018.01120
Dewey Decimal Classification:6 Technik, Medizin, angewandte Wissenschaften / 61 Medizin und Gesundheit / 610 Medizin und Gesundheit
Tag:GPX4; allosterism; anti-inflammatory; arachidonic acid metabolic network; drug discovery; enzyme activator; ferroptosis
Release Date:2020/10/20
Date of first Publication:2018/10/03
Licence (German):License LogoCC BY: Creative-Commons-Lizenz: Namensnennung 4.0 International