Glutaredoxin 2 protects cardiomyocytes from hypoxia/reoxygenation-induced injury by suppressing apoptosis, oxidative stress, and inflammation via enhancing Nrf2 signaling
Copyright © 2021 Elsevier B.V. All rights reserved..
Glutaredoxin 2 (GRX2) plays a cytoprotective role under various pathological conditions. However, whether GRX2 plays a role during myocardial ischemia-reperfusion injury has not been fully elucidated. In this work, we aimed to explore the detailed role and mechanism of GRX2 in modulating hypoxia/reoxygenation (H/R)-induced cardiac injury in vitro. H/R treatment resulted in a significant increase in GRX2 expression in cardiomyocytes. GRX2 knockdown enhanced the sensitivity of cardiomyocytes to H/R-induced apoptosis, oxidative stress, and inflammation, while GRX2 up-regulation exerted a cardioprotective role in H/R-injured cardiomyocytes. Further investigations revealed that GRX2 up-regulation enhanced the activation of nuclear factor erythroid 2-related factor 2 (Nrf2) signaling associated with upregulation of the phosphorylation of Akt and glycogen synthase kinase-3β (GSK-3β). Akt inhibition markedly abolished GRX2-mediated activation of Nrf2, while GSK-3β inhibition reversed GRX2-knockdown-mediated inhibition of Nrf2. In addition, Nrf2 inhibition markedly abrogated GRX2-mediated protective effects against H/R-induced apoptosis, oxidative stress and inflammation. Overall, this work indicates that GRX2 protects cardiomyocytes from H/R-induced apoptosis, oxidative stress, and inflammation by enhancing Nrf2 activation via modulation of the Akt/GSK-3β axis. Our study highlights a potential relevance of GRX2 in myocardial ischemia-reperfusion injury; it may serve as an attractive target for cardioprotection.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2021 |
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| Erschienen: |
2021 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:94 |
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| Enthalten in: |
International immunopharmacology - 94(2021) vom: 05. Mai, Seite 107428 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Li, Chengliang [VerfasserIn] |
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| Links: |
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| Anmerkungen: |
Date Completed 22.06.2021 Date Revised 22.06.2021 published: Print-Electronic Citation Status MEDLINE |
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| doi: |
10.1016/j.intimp.2021.107428 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| 520 | |a Glutaredoxin 2 (GRX2) plays a cytoprotective role under various pathological conditions. However, whether GRX2 plays a role during myocardial ischemia-reperfusion injury has not been fully elucidated. In this work, we aimed to explore the detailed role and mechanism of GRX2 in modulating hypoxia/reoxygenation (H/R)-induced cardiac injury in vitro. H/R treatment resulted in a significant increase in GRX2 expression in cardiomyocytes. GRX2 knockdown enhanced the sensitivity of cardiomyocytes to H/R-induced apoptosis, oxidative stress, and inflammation, while GRX2 up-regulation exerted a cardioprotective role in H/R-injured cardiomyocytes. Further investigations revealed that GRX2 up-regulation enhanced the activation of nuclear factor erythroid 2-related factor 2 (Nrf2) signaling associated with upregulation of the phosphorylation of Akt and glycogen synthase kinase-3β (GSK-3β). Akt inhibition markedly abolished GRX2-mediated activation of Nrf2, while GSK-3β inhibition reversed GRX2-knockdown-mediated inhibition of Nrf2. In addition, Nrf2 inhibition markedly abrogated GRX2-mediated protective effects against H/R-induced apoptosis, oxidative stress and inflammation. Overall, this work indicates that GRX2 protects cardiomyocytes from H/R-induced apoptosis, oxidative stress, and inflammation by enhancing Nrf2 activation via modulation of the Akt/GSK-3β axis. Our study highlights a potential relevance of GRX2 in myocardial ischemia-reperfusion injury; it may serve as an attractive target for cardioprotection | ||
| 650 | 4 | |a Journal Article | |
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| 650 | 4 | |a Hypoxia/reoxygenation | |
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