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Gluconolactone Alleviates Myocardial Ischemia/Reperfusion Injury and Arrhythmias via Activating PKCε/Extracellular Signal-Regulated Kinase Signaling
Gluconolactone (D-glucono-1,5-lactone or GDL) is a food additive which presents in dietary products such as tofu, yogurt, cheese, bread, wine, etc. GDL has long been considered as a free radical scavenger; however, its role in cardioprotection remains elusive. In this study, using a mouse model of m...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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Frontiers Media S.A.
2022
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8964113/ https://www.ncbi.nlm.nih.gov/pubmed/35360251 http://dx.doi.org/10.3389/fphys.2022.856699 |
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author | Qin, Xinghua Liu, Binghua Gao, Feng Hu, Yuanyuan Chen, Ziwei Xu, Jie Zhang, Xing |
author_facet | Qin, Xinghua Liu, Binghua Gao, Feng Hu, Yuanyuan Chen, Ziwei Xu, Jie Zhang, Xing |
author_sort | Qin, Xinghua |
collection | PubMed |
description | Gluconolactone (D-glucono-1,5-lactone or GDL) is a food additive which presents in dietary products such as tofu, yogurt, cheese, bread, wine, etc. GDL has long been considered as a free radical scavenger; however, its role in cardioprotection remains elusive. In this study, using a mouse model of myocardial ischemia/reperfusion (I/R) injury and a model of hypoxia/reoxygenation (H/R) in neonatal rat cardiomyocytes (NRCM), we explored the role of GDL in I/R injury. We found that GDL (5 mg/kg, i.p.) attenuated myocardial I/R injury as evidenced by decreased infarct size, release of cardiac injury markers and apoptosis. Additionally, GDL decreased reperfusion-induced arrhythmias and oxidative stress. These effects were also observed in parallel in vitro studies. Mechanistically, we found that GDL treatment was strongly associated with activation of pro-survival extracellular signal-regulated kinase (ERK) signaling both in vivo and in vitro, and pharmacological inhibition of ERK signaling via U0126 attenuated GDL-induced cardioprotection against H/R injury in NRCM cells. To reveal how GDL regulates ERK signaling, we predicted the putative targets of GDL by Swiss Target Prediction, and protein kinase C (PKC) emerged as the most promising target for GDL. By pharmacological intervention and immunofluorescence, we found that PKCε, an important member of the PKC family, was activated after GDL treatment in heart, thereby leading to ERK activation and cardioprotection against I/R injury. Taken together, our results demonstrated that GDL acts as a potent activator of PKCε and, thus, provides cardioprotection against I/R injury via activation of ERK signaling. |
format | Online Article Text |
id | pubmed-8964113 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-89641132022-03-30 Gluconolactone Alleviates Myocardial Ischemia/Reperfusion Injury and Arrhythmias via Activating PKCε/Extracellular Signal-Regulated Kinase Signaling Qin, Xinghua Liu, Binghua Gao, Feng Hu, Yuanyuan Chen, Ziwei Xu, Jie Zhang, Xing Front Physiol Physiology Gluconolactone (D-glucono-1,5-lactone or GDL) is a food additive which presents in dietary products such as tofu, yogurt, cheese, bread, wine, etc. GDL has long been considered as a free radical scavenger; however, its role in cardioprotection remains elusive. In this study, using a mouse model of myocardial ischemia/reperfusion (I/R) injury and a model of hypoxia/reoxygenation (H/R) in neonatal rat cardiomyocytes (NRCM), we explored the role of GDL in I/R injury. We found that GDL (5 mg/kg, i.p.) attenuated myocardial I/R injury as evidenced by decreased infarct size, release of cardiac injury markers and apoptosis. Additionally, GDL decreased reperfusion-induced arrhythmias and oxidative stress. These effects were also observed in parallel in vitro studies. Mechanistically, we found that GDL treatment was strongly associated with activation of pro-survival extracellular signal-regulated kinase (ERK) signaling both in vivo and in vitro, and pharmacological inhibition of ERK signaling via U0126 attenuated GDL-induced cardioprotection against H/R injury in NRCM cells. To reveal how GDL regulates ERK signaling, we predicted the putative targets of GDL by Swiss Target Prediction, and protein kinase C (PKC) emerged as the most promising target for GDL. By pharmacological intervention and immunofluorescence, we found that PKCε, an important member of the PKC family, was activated after GDL treatment in heart, thereby leading to ERK activation and cardioprotection against I/R injury. Taken together, our results demonstrated that GDL acts as a potent activator of PKCε and, thus, provides cardioprotection against I/R injury via activation of ERK signaling. Frontiers Media S.A. 2022-03-14 /pmc/articles/PMC8964113/ /pubmed/35360251 http://dx.doi.org/10.3389/fphys.2022.856699 Text en Copyright © 2022 Qin, Liu, Gao, Hu, Chen, Xu and Zhang. https://creativecommons.org/licenses/by/4.0/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. |
spellingShingle | Physiology Qin, Xinghua Liu, Binghua Gao, Feng Hu, Yuanyuan Chen, Ziwei Xu, Jie Zhang, Xing Gluconolactone Alleviates Myocardial Ischemia/Reperfusion Injury and Arrhythmias via Activating PKCε/Extracellular Signal-Regulated Kinase Signaling |
title | Gluconolactone Alleviates Myocardial Ischemia/Reperfusion Injury and Arrhythmias via Activating PKCε/Extracellular Signal-Regulated Kinase Signaling |
title_full | Gluconolactone Alleviates Myocardial Ischemia/Reperfusion Injury and Arrhythmias via Activating PKCε/Extracellular Signal-Regulated Kinase Signaling |
title_fullStr | Gluconolactone Alleviates Myocardial Ischemia/Reperfusion Injury and Arrhythmias via Activating PKCε/Extracellular Signal-Regulated Kinase Signaling |
title_full_unstemmed | Gluconolactone Alleviates Myocardial Ischemia/Reperfusion Injury and Arrhythmias via Activating PKCε/Extracellular Signal-Regulated Kinase Signaling |
title_short | Gluconolactone Alleviates Myocardial Ischemia/Reperfusion Injury and Arrhythmias via Activating PKCε/Extracellular Signal-Regulated Kinase Signaling |
title_sort | gluconolactone alleviates myocardial ischemia/reperfusion injury and arrhythmias via activating pkcε/extracellular signal-regulated kinase signaling |
topic | Physiology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8964113/ https://www.ncbi.nlm.nih.gov/pubmed/35360251 http://dx.doi.org/10.3389/fphys.2022.856699 |
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