Redox RegulationviaGlutaredoxin-1 and ProteinS-Glutathionylation
| Autor: | Reiko Matsui, Beatriz Ferrán, Albin Oh, Di Shao, Dominique Croteau, Markus Bachschmid, Jingyan Han, David R. Pimentel |
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| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
Antioxidant Physiology medicine.medical_treatment Clinical Biochemistry Oxidative phosphorylation medicine.disease_cause Biochemistry 03 medical and health sciences chemistry.chemical_compound Glutaredoxin medicine Molecular Biology General Environmental Science chemistry.chemical_classification Reactive oxygen species 030102 biochemistry & molecular biology Cell Biology Glutathione Cell biology 030104 developmental biology chemistry General Earth and Planetary Sciences Sulfenic acid Oxidative stress Cysteine |
| Zdroj: | Antioxidants & Redox Signaling. 32:677-700 |
| ISSN: | 1557-7716 1523-0864 |
| DOI: | 10.1089/ars.2019.7963 |
| Popis: | Significance: Over the past several years, oxidative post-translational modifications of protein cysteines have been recognized for their critical roles in physiology and pathophysiology. Cells have harnessed thiol modifications involving both oxidative and reductive steps for signaling and protein processing. One of these stages requires oxidation of cysteine to sulfenic acid, followed by two reduction reactions. First, glutathione (reduced glutathione [GSH]) forms a S-glutathionylated protein, and second, enzymatic or chemical reduction removes the modification. Under physiological conditions, these steps confer redox signaling and protect cysteines from irreversible oxidation. However, oxidative stress can overwhelm protein S-glutathionylation and irreversibly modify cysteine residues, disrupting redox signaling. Critical Issues: Glutaredoxins mainly catalyze the removal of protein-bound GSH and help maintain protein thiols in a highly reduced state without exerting direct antioxidant properties. Conversely, glutathione S-transferase (GST), peroxiredoxins, and occasionally glutaredoxins can also catalyze protein S-glutathionylation, thus promoting a dynamic redox environment. Recent Advances: The latest studies of glutaredoxin-1 (Glrx) transgenic or knockout mice demonstrate important distinct roles of Glrx in a variety of pathologies. Endogenous Glrx is essential to maintain normal hepatic lipid homeostasis and prevent fatty liver disease. Further, in vivo deletion of Glrx protects lungs from inflammation and bacterial pneumonia-induced damage, attenuates angiotensin II-induced cardiovascular hypertrophy, and improves ischemic limb vascularization. Meanwhile, exogenous Glrx administration can reverse pathological lung fibrosis. Future Directions: Although S-glutathionylation modifies many proteins, these studies suggest that S-glutathionylation and Glrx regulate specific pathways in vivo, and they implicate Glrx as a potential novel therapeutic target to treat diverse disease conditions. Antioxid. Redox Signal. 32, 677-700. |
| Databáze: | OpenAIRE |
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