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Cyclophilin A Protects Cardiomyocytes against Hypoxia/Reoxygenation-Induced Apoptosis via the AKT/Nox2 Pathway
Hypoxia/reoxygenation (H/R) accelerates the process of cardiomyocyte apoptosis during ischemia-reperfusion. Excessive reactive oxygen species (ROS) are a critical driver of oxidative stress injury. Cyclophilin A (CyPA) is a major ROS-induced factor in atherosclerosis. There is a positive feedback me...
Autores principales: | , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Hindawi
2019
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6512079/ https://www.ncbi.nlm.nih.gov/pubmed/31182989 http://dx.doi.org/10.1155/2019/2717986 |
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author | Cheng, Fuyu Yuan, Wei Cao, Mengfei Chen, Rui Wu, Xiuli Yan, Jinchuan |
author_facet | Cheng, Fuyu Yuan, Wei Cao, Mengfei Chen, Rui Wu, Xiuli Yan, Jinchuan |
author_sort | Cheng, Fuyu |
collection | PubMed |
description | Hypoxia/reoxygenation (H/R) accelerates the process of cardiomyocyte apoptosis during ischemia-reperfusion. Excessive reactive oxygen species (ROS) are a critical driver of oxidative stress injury. Cyclophilin A (CyPA) is a major ROS-induced factor in atherosclerosis. There is a positive feedback mechanism between CyPA and ROS, which enables the oxidative stress response to continue and expand. However, it is unclear whether this positive feedback mechanism exists in cardiomyocytes. Through western blotting and flow cytometric assays and TUNEL assay, we found that CyPA inhibited the apoptosis of H9c2 cardiomyocytes under H/R conditions. By dihydroethidium (DHE) staining and electron spin resonance (ESR) assays, we demonstrated that CyPA reduced ROS production and suppressed O(2)(−) production dependent on reduced nicotinamide adenine dinucleotide phosphate (NADPH) oxidase. By western blotting, we showed that CyPA inhibited the expression of NADPH oxidase 2 (Nox2) protein by the AKT pathway. Through confocal microscopy assay, we found that CyPA reduced the expression of Nox2 membrane-bound subunits. The current study shows that a positive feedback mechanism does not exist in H9c2 cardiomyoblasts. CyPA protects H9c2 cardiomyoblasts against H/R-induced apoptosis via the AKT/Nox2 pathway. This could be a potential target for ischemia-reperfusion injury therapy. |
format | Online Article Text |
id | pubmed-6512079 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | Hindawi |
record_format | MEDLINE/PubMed |
spelling | pubmed-65120792019-06-10 Cyclophilin A Protects Cardiomyocytes against Hypoxia/Reoxygenation-Induced Apoptosis via the AKT/Nox2 Pathway Cheng, Fuyu Yuan, Wei Cao, Mengfei Chen, Rui Wu, Xiuli Yan, Jinchuan Oxid Med Cell Longev Research Article Hypoxia/reoxygenation (H/R) accelerates the process of cardiomyocyte apoptosis during ischemia-reperfusion. Excessive reactive oxygen species (ROS) are a critical driver of oxidative stress injury. Cyclophilin A (CyPA) is a major ROS-induced factor in atherosclerosis. There is a positive feedback mechanism between CyPA and ROS, which enables the oxidative stress response to continue and expand. However, it is unclear whether this positive feedback mechanism exists in cardiomyocytes. Through western blotting and flow cytometric assays and TUNEL assay, we found that CyPA inhibited the apoptosis of H9c2 cardiomyocytes under H/R conditions. By dihydroethidium (DHE) staining and electron spin resonance (ESR) assays, we demonstrated that CyPA reduced ROS production and suppressed O(2)(−) production dependent on reduced nicotinamide adenine dinucleotide phosphate (NADPH) oxidase. By western blotting, we showed that CyPA inhibited the expression of NADPH oxidase 2 (Nox2) protein by the AKT pathway. Through confocal microscopy assay, we found that CyPA reduced the expression of Nox2 membrane-bound subunits. The current study shows that a positive feedback mechanism does not exist in H9c2 cardiomyoblasts. CyPA protects H9c2 cardiomyoblasts against H/R-induced apoptosis via the AKT/Nox2 pathway. This could be a potential target for ischemia-reperfusion injury therapy. Hindawi 2019-04-28 /pmc/articles/PMC6512079/ /pubmed/31182989 http://dx.doi.org/10.1155/2019/2717986 Text en Copyright © 2019 Fuyu Cheng et al. http://creativecommons.org/licenses/by/4.0/ This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Research Article Cheng, Fuyu Yuan, Wei Cao, Mengfei Chen, Rui Wu, Xiuli Yan, Jinchuan Cyclophilin A Protects Cardiomyocytes against Hypoxia/Reoxygenation-Induced Apoptosis via the AKT/Nox2 Pathway |
title | Cyclophilin A Protects Cardiomyocytes against Hypoxia/Reoxygenation-Induced Apoptosis via the AKT/Nox2 Pathway |
title_full | Cyclophilin A Protects Cardiomyocytes against Hypoxia/Reoxygenation-Induced Apoptosis via the AKT/Nox2 Pathway |
title_fullStr | Cyclophilin A Protects Cardiomyocytes against Hypoxia/Reoxygenation-Induced Apoptosis via the AKT/Nox2 Pathway |
title_full_unstemmed | Cyclophilin A Protects Cardiomyocytes against Hypoxia/Reoxygenation-Induced Apoptosis via the AKT/Nox2 Pathway |
title_short | Cyclophilin A Protects Cardiomyocytes against Hypoxia/Reoxygenation-Induced Apoptosis via the AKT/Nox2 Pathway |
title_sort | cyclophilin a protects cardiomyocytes against hypoxia/reoxygenation-induced apoptosis via the akt/nox2 pathway |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6512079/ https://www.ncbi.nlm.nih.gov/pubmed/31182989 http://dx.doi.org/10.1155/2019/2717986 |
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