Cargando…

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...

Descripción completa

Detalles Bibliográficos
Autores principales: Qin, Xinghua, Liu, Binghua, Gao, Feng, Hu, Yuanyuan, Chen, Ziwei, Xu, Jie, Zhang, Xing
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2022
Materias:
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
_version_ 1784678138813349888
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
work_keys_str_mv AT qinxinghua gluconolactonealleviatesmyocardialischemiareperfusioninjuryandarrhythmiasviaactivatingpkceextracellularsignalregulatedkinasesignaling
AT liubinghua gluconolactonealleviatesmyocardialischemiareperfusioninjuryandarrhythmiasviaactivatingpkceextracellularsignalregulatedkinasesignaling
AT gaofeng gluconolactonealleviatesmyocardialischemiareperfusioninjuryandarrhythmiasviaactivatingpkceextracellularsignalregulatedkinasesignaling
AT huyuanyuan gluconolactonealleviatesmyocardialischemiareperfusioninjuryandarrhythmiasviaactivatingpkceextracellularsignalregulatedkinasesignaling
AT chenziwei gluconolactonealleviatesmyocardialischemiareperfusioninjuryandarrhythmiasviaactivatingpkceextracellularsignalregulatedkinasesignaling
AT xujie gluconolactonealleviatesmyocardialischemiareperfusioninjuryandarrhythmiasviaactivatingpkceextracellularsignalregulatedkinasesignaling
AT zhangxing gluconolactonealleviatesmyocardialischemiareperfusioninjuryandarrhythmiasviaactivatingpkceextracellularsignalregulatedkinasesignaling