Glatiramer acetate protects against oxygen-glucose deprivation/reperfusion-induced injury by inhibiting Egr-1 in H9c2 cells.

Abstract

Myocardial infarction (MI) or heart attack is a deadly event with high prevalence. In the present study, we investigated the effects of the polypeptide copolymer glatiramer acetate (GA) in H9c2 rat cardiomyocytes exposed to oxygen-glucose deprivation/reperfusion injury. Immediately following MI, an acute inflammatory response is triggered that causes activation of various proinflammatory cytokines, infiltration of immune cells, and neovascularization. This response is largely mediated by some genes such as TNF-α, IL-6, ICAM-1, and VEGF. Additionally, the rapid influx of oxidants, such as reactive oxygen species (ROS), leads to a harmful state of oxidative stress. Here, we found that GA could reduce OGD/R-induced inflammation and oxidative stress by inhibiting the expression of TNF-α, IL-6, ICAM-1, and VEGF, and suppressing the production of ROS via reduced NADPH oxidase 1 (NOX1) expression. To elucidate the pathways involved in these promising results, we took a close look at the impact of the endothelial growth response-1 (Egr-1), a transcriptional factor recognized as a mediator of MI-related inflammation and cellular injury. Using siRNA for Egr-1, we found that GA could reduce the expression of ICAM-1 and VEGF by inhibiting Egr-1 expression. Together, our findings indicate a novel therapeutic potential of GA in the treatment of MI.

• Authors: Jian Du, Wei Lv, Sitong Yang, Jia Liu, Juan Zhen, Jiyan Leng
• Journal: Molecular immunology (Mol Immunol) Vol. 120 Pg. 61-66 (04 2020) ISSN: 1872-9142 [Electronic] England
• PMID: 32078859 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2020 Elsevier Ltd. All rights reserved.

Chemical References

• Cardiotonic Agents
• Early Growth Response Protein 1
• Egr1 protein, rat
• Inflammation Mediators
• RNA, Messenger
• Reactive Oxygen Species
• Glatiramer Acetate
• Glucose
• Oxygen

Topics

• Animals
• Cardiotonic Agents (pharmacology)
• Cell Line
• Early Growth Response Protein 1 (antagonists & inhibitors, genetics, metabolism)
• Glatiramer Acetate (pharmacology)
• Glucose (metabolism)
• Inflammation Mediators (antagonists & inhibitors, metabolism)
• Myocardial Infarction (drug therapy, genetics, metabolism)
• Myocardial Reperfusion Injury (drug therapy, metabolism, prevention & control)
• Myocytes, Cardiac (drug effects, metabolism)
• Oxidative Stress (drug effects)
• Oxygen (metabolism)
• RNA, Messenger (genetics, metabolism)
• Rats
• Reactive Oxygen Species (metabolism)