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Exenatide Reduces Tumor Necrosis Factor-α-induced Apoptosis in Cardiomyocytes by Alleviating Mitochondrial Dysfunction
BACKGROUND: Tumor necrosis factor-α (TNF-α) plays an important role in progressive contractile dysfunction in several cardiac diseases. The cytotoxic effects of TNF-α are suggested to be partly mediated by reactive oxygen species (ROS)- and mitochondria-dependent apoptosis. Glucagon-like peptide-1 (...
Autores principales: | , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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Medknow Publications & Media Pvt Ltd
2015
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4794880/ https://www.ncbi.nlm.nih.gov/pubmed/26612298 http://dx.doi.org/10.4103/0366-6999.170259 |
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author | Cao, Yuan-Yuan Chen, Zhang-Wei Gao, Yan-Hua Wang, Xing-Xu Ma, Jian-Ying Chang, Shu-Fu Qian, Ju-Ying Ge, Jun-Bo |
author_facet | Cao, Yuan-Yuan Chen, Zhang-Wei Gao, Yan-Hua Wang, Xing-Xu Ma, Jian-Ying Chang, Shu-Fu Qian, Ju-Ying Ge, Jun-Bo |
author_sort | Cao, Yuan-Yuan |
collection | PubMed |
description | BACKGROUND: Tumor necrosis factor-α (TNF-α) plays an important role in progressive contractile dysfunction in several cardiac diseases. The cytotoxic effects of TNF-α are suggested to be partly mediated by reactive oxygen species (ROS)- and mitochondria-dependent apoptosis. Glucagon-like peptide-1 (GLP-1) or its analogue exhibits protective effects on the cardiovascular system. The objective of the study was to assess the effects of exenatide, a GLP-1 analogue, on oxidative stress, and apoptosis in TNF-α-treated cardiomyocytes in vitro. METHODS: Isolated neonatal rat cardiomyocytes were divided into three groups: Control group, with cells cultured in normal conditions without intervention; TNF-α group, with cells incubated with TNF-α (40 ng/ml) for 6, 12, or 24 h without pretreatment with exenatide; and exenatide group, with cells pretreated with exenatide (100 nmol/L) 30 mins before TNF-α (40 ng/ml) stimulation. We evaluated apoptosis by terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) assay and flow cytometry, measured ROS production and mitochondrial membrane potential (MMP) by specific the fluorescent probes, and assessed the levels of proteins by Western blotting for all the groups. RESULTS: Exenatide pretreatment significantly reduced cardiomyocyte apoptosis as measured by flow cytometry and TUNEL assay at 12 h and 24 h. Also, exenatide inhibited excessive ROS production and maintained MMP. Furthermore, declined cytochrome-c release and cleaved caspase-3 expression and increased bcl-2 expression with concomitantly decreased Bax activation were observed in exenatide-pretreated cultures. CONCLUSION: These results suggested that exenatide exerts a protective effect on cardiomyocytes, preventing TNF-α-induced apoptosis; the anti-apoptotic effects may be associated with protection of mitochondrial function. |
format | Online Article Text |
id | pubmed-4794880 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2015 |
publisher | Medknow Publications & Media Pvt Ltd |
record_format | MEDLINE/PubMed |
spelling | pubmed-47948802016-04-04 Exenatide Reduces Tumor Necrosis Factor-α-induced Apoptosis in Cardiomyocytes by Alleviating Mitochondrial Dysfunction Cao, Yuan-Yuan Chen, Zhang-Wei Gao, Yan-Hua Wang, Xing-Xu Ma, Jian-Ying Chang, Shu-Fu Qian, Ju-Ying Ge, Jun-Bo Chin Med J (Engl) Original Article BACKGROUND: Tumor necrosis factor-α (TNF-α) plays an important role in progressive contractile dysfunction in several cardiac diseases. The cytotoxic effects of TNF-α are suggested to be partly mediated by reactive oxygen species (ROS)- and mitochondria-dependent apoptosis. Glucagon-like peptide-1 (GLP-1) or its analogue exhibits protective effects on the cardiovascular system. The objective of the study was to assess the effects of exenatide, a GLP-1 analogue, on oxidative stress, and apoptosis in TNF-α-treated cardiomyocytes in vitro. METHODS: Isolated neonatal rat cardiomyocytes were divided into three groups: Control group, with cells cultured in normal conditions without intervention; TNF-α group, with cells incubated with TNF-α (40 ng/ml) for 6, 12, or 24 h without pretreatment with exenatide; and exenatide group, with cells pretreated with exenatide (100 nmol/L) 30 mins before TNF-α (40 ng/ml) stimulation. We evaluated apoptosis by terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) assay and flow cytometry, measured ROS production and mitochondrial membrane potential (MMP) by specific the fluorescent probes, and assessed the levels of proteins by Western blotting for all the groups. RESULTS: Exenatide pretreatment significantly reduced cardiomyocyte apoptosis as measured by flow cytometry and TUNEL assay at 12 h and 24 h. Also, exenatide inhibited excessive ROS production and maintained MMP. Furthermore, declined cytochrome-c release and cleaved caspase-3 expression and increased bcl-2 expression with concomitantly decreased Bax activation were observed in exenatide-pretreated cultures. CONCLUSION: These results suggested that exenatide exerts a protective effect on cardiomyocytes, preventing TNF-α-induced apoptosis; the anti-apoptotic effects may be associated with protection of mitochondrial function. Medknow Publications & Media Pvt Ltd 2015-12-05 /pmc/articles/PMC4794880/ /pubmed/26612298 http://dx.doi.org/10.4103/0366-6999.170259 Text en Copyright: © 2015 Chinese Medical Journal http://creativecommons.org/licenses/by-nc-sa/3.0 This is an open access article distributed under the terms of the Creative Commons Attribution-NonCommercial-ShareAlike 3.0 License, which allows others to remix, tweak, and build upon the work non-commercially, as long as the author is credited and the new creations are licensed under the identical terms. |
spellingShingle | Original Article Cao, Yuan-Yuan Chen, Zhang-Wei Gao, Yan-Hua Wang, Xing-Xu Ma, Jian-Ying Chang, Shu-Fu Qian, Ju-Ying Ge, Jun-Bo Exenatide Reduces Tumor Necrosis Factor-α-induced Apoptosis in Cardiomyocytes by Alleviating Mitochondrial Dysfunction |
title | Exenatide Reduces Tumor Necrosis Factor-α-induced Apoptosis in Cardiomyocytes by Alleviating Mitochondrial Dysfunction |
title_full | Exenatide Reduces Tumor Necrosis Factor-α-induced Apoptosis in Cardiomyocytes by Alleviating Mitochondrial Dysfunction |
title_fullStr | Exenatide Reduces Tumor Necrosis Factor-α-induced Apoptosis in Cardiomyocytes by Alleviating Mitochondrial Dysfunction |
title_full_unstemmed | Exenatide Reduces Tumor Necrosis Factor-α-induced Apoptosis in Cardiomyocytes by Alleviating Mitochondrial Dysfunction |
title_short | Exenatide Reduces Tumor Necrosis Factor-α-induced Apoptosis in Cardiomyocytes by Alleviating Mitochondrial Dysfunction |
title_sort | exenatide reduces tumor necrosis factor-α-induced apoptosis in cardiomyocytes by alleviating mitochondrial dysfunction |
topic | Original Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4794880/ https://www.ncbi.nlm.nih.gov/pubmed/26612298 http://dx.doi.org/10.4103/0366-6999.170259 |
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