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Protective Effects and Mechanisms of Recombinant Human Glutathione Peroxidase 4 on Isoproterenol-Induced Myocardial Ischemia Injury.

Abstract
Ischemic heart disease (IHD) is a cardiovascular disease with high fatality rate, and its pathogenesis is closely related to oxidative stress. Reactive oxygen species (ROS) in oxidative stress can lead to myocardial ischemia (MI) injury in many ways. Therefore, the application of antioxidants may be an effective way to prevent IHD. In recent years, glutathione peroxidase 4 (GPx4) has received increasing attention due to its antioxidant effect. In a previous study, we used the new chimeric tRNAUTuT6 to express highly active recombinant human GPx4 (rhGPx4) in amber-less Escherichia coli. In this study, we established an isoproterenol- (ISO-) induced MI injury model in rats and an in vitro model to research the protective effect and mechanism of rhGPx4 on MI injury. The results showed that rhGPx4 could reduce the area of myocardial infarction and ameliorate the pathological injury of heart tissue, significantly reduce ISO-induced abnormalities on electrocardiogram (ECG) and cardiac serum biomarkers, protect mitochondrial function, and attenuate cardiac oxidative stress injury. In an in vitro model, the results also confirmed that rhGPx4 could inhibit ISO-induced oxidative stress injury and cardiomyocyte apoptosis. The mechanism of action of rhGPx4 involves not only the inhibition of lipid peroxidation by eliminating ROS but also keeping a normal level of endogenous antioxidant enzymes by eliminating ROS, thereby preventing oxidative stress injury in cardiomyocytes. Additionally, rhGPx4 could inhibit cardiomyocyte apoptosis through a mitochondria-dependent pathway. In short, rhGPx4, a recombinant antioxidant enzyme, can play an important role in the prevention of IHD and may have great potential for application.
AuthorsChang Liu, Bozhao Li, Qi Yan, Shaopeng Niu, Yiding Zhao, Changhao Xiong, Tianjiao Zhang, Jingyan Wei
JournalOxidative medicine and cellular longevity (Oxid Med Cell Longev) Vol. 2021 Pg. 6632813 ( 2021) ISSN: 1942-0994 [Electronic] United States
PMID34539971 (Publication Type: Journal Article)
CopyrightCopyright © 2021 Chang Liu et al.
Chemical References
  • Biomarkers
  • Protective Agents
  • Reactive Oxygen Species
  • Recombinant Proteins
  • Troponin T
  • Phospholipid Hydroperoxide Glutathione Peroxidase
  • Isoproterenol
Topics
  • Animals
  • Apoptosis (drug effects)
  • Biomarkers (blood)
  • Cell Line
  • Disease Models, Animal
  • Electrocardiography
  • Humans
  • Isoproterenol (toxicity)
  • Male
  • Membrane Potential, Mitochondrial (drug effects)
  • Myocardial Infarction (chemically induced, drug therapy, metabolism)
  • Myocytes, Cardiac (cytology, drug effects, metabolism)
  • Oxidative Stress (drug effects)
  • Phospholipid Hydroperoxide Glutathione Peroxidase (genetics, metabolism, pharmacology, therapeutic use)
  • Protective Agents (pharmacology, therapeutic use)
  • Rats
  • Rats, Sprague-Dawley
  • Reactive Oxygen Species (metabolism)
  • Recombinant Proteins (biosynthesis, pharmacology, therapeutic use)
  • Troponin T (blood)

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