Original Research ARTICLE
Activation of Glutathione Peroxidase 4 as a Novel Anti-Inflammatory Strategy
- 1College of Chemistry, Peking University, China
- 2Center for Quantitative Biology, Peking University, China
- 3Peking−Tsinghua Center for Life Sciences, Peking University, China
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 arachidonic acid 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.
Keywords: arachidonic acid metabolic network, GPx4, Enzyme activator, allosterism, Drug Discovery, anti-inflammatory, ferroptosis
Received: 14 Apr 2018;
Accepted: 13 Sep 2018.
Edited by:Honglin Li, East China University of Science and Technology, China
Reviewed by:Carsten Culmsee, Philipps-Universität Marburg, Germany
Zhijun Xie, Zhejiang Chinese Medical University, China
Copyright: © 2018 Li, Deng, Xie, Liu and Lai. 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.
* Correspondence: Prof. Luhua Lai, Peking University, College of Chemistry, Beijing, China, firstname.lastname@example.org