Cargando…
The Histone Deacetylase Inhibitor Suberoylanilide Hydroxamic Acid (SAHA) Restores Cardiomyocyte Contractility in a Rat Model of Early Diabetes
In early diabetes, hyperglycemia and the associated metabolic dysregulation promote early changes in the functional properties of cardiomyocytes, progressively leading to the appearance of the diabetic cardiomyopathy phenotype. Recently, the interplay between histone acetyltransferases (HAT) and his...
Autores principales: | , , , , , , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2019
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6514644/ https://www.ncbi.nlm.nih.gov/pubmed/31014028 http://dx.doi.org/10.3390/ijms20081873 |
_version_ | 1783417908883357696 |
---|---|
author | Bocchi, Leonardo Motta, Benedetta M. Savi, Monia Vilella, Rocchina Meraviglia, Viviana Rizzi, Federica Galati, Serena Buschini, Annamaria Lazzaretti, Mirca Pramstaller, Peter P. Rossini, Alessandra Stilli, Donatella |
author_facet | Bocchi, Leonardo Motta, Benedetta M. Savi, Monia Vilella, Rocchina Meraviglia, Viviana Rizzi, Federica Galati, Serena Buschini, Annamaria Lazzaretti, Mirca Pramstaller, Peter P. Rossini, Alessandra Stilli, Donatella |
author_sort | Bocchi, Leonardo |
collection | PubMed |
description | In early diabetes, hyperglycemia and the associated metabolic dysregulation promote early changes in the functional properties of cardiomyocytes, progressively leading to the appearance of the diabetic cardiomyopathy phenotype. Recently, the interplay between histone acetyltransferases (HAT) and histone deacetylases (HDAC) has emerged as a crucial factor in the development of cardiac disorders. The present study evaluates whether HDAC inhibition can prevent the development of cardiomyocyte contractile dysfunction induced by a short period of hyperglycemia, with focus on the potential underlying mechanisms. Cell contractility and calcium dynamics were measured in unloaded ventricular myocytes isolated from the heart of control and diabetic rats. Cardiomyocytes were either untreated or exposed to the pan-HDAC inhibitor suberoylanilide hydroxamic acid (SAHA) for 90 min. Then, a fraction of each group of cells was used to evaluate the expression levels of proteins involved in the excitation–contraction coupling, and the cardiomyocyte metabolic activity, ATP content, and reactive oxygen species levels. SAHA treatment was able to counteract the initial functional derangement in cardiomyocytes by reducing cell oxidative damage. These findings suggest that early HDAC inhibition could be a promising adjuvant approach for preventing diabetes-induced cardiomyocyte oxidative damage, which triggers the pro-inflammatory signal cascade, mitochondrial damage, and ventricular dysfunction. |
format | Online Article Text |
id | pubmed-6514644 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-65146442019-05-30 The Histone Deacetylase Inhibitor Suberoylanilide Hydroxamic Acid (SAHA) Restores Cardiomyocyte Contractility in a Rat Model of Early Diabetes Bocchi, Leonardo Motta, Benedetta M. Savi, Monia Vilella, Rocchina Meraviglia, Viviana Rizzi, Federica Galati, Serena Buschini, Annamaria Lazzaretti, Mirca Pramstaller, Peter P. Rossini, Alessandra Stilli, Donatella Int J Mol Sci Article In early diabetes, hyperglycemia and the associated metabolic dysregulation promote early changes in the functional properties of cardiomyocytes, progressively leading to the appearance of the diabetic cardiomyopathy phenotype. Recently, the interplay between histone acetyltransferases (HAT) and histone deacetylases (HDAC) has emerged as a crucial factor in the development of cardiac disorders. The present study evaluates whether HDAC inhibition can prevent the development of cardiomyocyte contractile dysfunction induced by a short period of hyperglycemia, with focus on the potential underlying mechanisms. Cell contractility and calcium dynamics were measured in unloaded ventricular myocytes isolated from the heart of control and diabetic rats. Cardiomyocytes were either untreated or exposed to the pan-HDAC inhibitor suberoylanilide hydroxamic acid (SAHA) for 90 min. Then, a fraction of each group of cells was used to evaluate the expression levels of proteins involved in the excitation–contraction coupling, and the cardiomyocyte metabolic activity, ATP content, and reactive oxygen species levels. SAHA treatment was able to counteract the initial functional derangement in cardiomyocytes by reducing cell oxidative damage. These findings suggest that early HDAC inhibition could be a promising adjuvant approach for preventing diabetes-induced cardiomyocyte oxidative damage, which triggers the pro-inflammatory signal cascade, mitochondrial damage, and ventricular dysfunction. MDPI 2019-04-16 /pmc/articles/PMC6514644/ /pubmed/31014028 http://dx.doi.org/10.3390/ijms20081873 Text en © 2019 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Bocchi, Leonardo Motta, Benedetta M. Savi, Monia Vilella, Rocchina Meraviglia, Viviana Rizzi, Federica Galati, Serena Buschini, Annamaria Lazzaretti, Mirca Pramstaller, Peter P. Rossini, Alessandra Stilli, Donatella The Histone Deacetylase Inhibitor Suberoylanilide Hydroxamic Acid (SAHA) Restores Cardiomyocyte Contractility in a Rat Model of Early Diabetes |
title | The Histone Deacetylase Inhibitor Suberoylanilide Hydroxamic Acid (SAHA) Restores Cardiomyocyte Contractility in a Rat Model of Early Diabetes |
title_full | The Histone Deacetylase Inhibitor Suberoylanilide Hydroxamic Acid (SAHA) Restores Cardiomyocyte Contractility in a Rat Model of Early Diabetes |
title_fullStr | The Histone Deacetylase Inhibitor Suberoylanilide Hydroxamic Acid (SAHA) Restores Cardiomyocyte Contractility in a Rat Model of Early Diabetes |
title_full_unstemmed | The Histone Deacetylase Inhibitor Suberoylanilide Hydroxamic Acid (SAHA) Restores Cardiomyocyte Contractility in a Rat Model of Early Diabetes |
title_short | The Histone Deacetylase Inhibitor Suberoylanilide Hydroxamic Acid (SAHA) Restores Cardiomyocyte Contractility in a Rat Model of Early Diabetes |
title_sort | histone deacetylase inhibitor suberoylanilide hydroxamic acid (saha) restores cardiomyocyte contractility in a rat model of early diabetes |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6514644/ https://www.ncbi.nlm.nih.gov/pubmed/31014028 http://dx.doi.org/10.3390/ijms20081873 |
work_keys_str_mv | AT bocchileonardo thehistonedeacetylaseinhibitorsuberoylanilidehydroxamicacidsaharestorescardiomyocytecontractilityinaratmodelofearlydiabetes AT mottabenedettam thehistonedeacetylaseinhibitorsuberoylanilidehydroxamicacidsaharestorescardiomyocytecontractilityinaratmodelofearlydiabetes AT savimonia thehistonedeacetylaseinhibitorsuberoylanilidehydroxamicacidsaharestorescardiomyocytecontractilityinaratmodelofearlydiabetes AT vilellarocchina thehistonedeacetylaseinhibitorsuberoylanilidehydroxamicacidsaharestorescardiomyocytecontractilityinaratmodelofearlydiabetes AT meravigliaviviana thehistonedeacetylaseinhibitorsuberoylanilidehydroxamicacidsaharestorescardiomyocytecontractilityinaratmodelofearlydiabetes AT rizzifederica thehistonedeacetylaseinhibitorsuberoylanilidehydroxamicacidsaharestorescardiomyocytecontractilityinaratmodelofearlydiabetes AT galatiserena thehistonedeacetylaseinhibitorsuberoylanilidehydroxamicacidsaharestorescardiomyocytecontractilityinaratmodelofearlydiabetes AT buschiniannamaria thehistonedeacetylaseinhibitorsuberoylanilidehydroxamicacidsaharestorescardiomyocytecontractilityinaratmodelofearlydiabetes AT lazzarettimirca thehistonedeacetylaseinhibitorsuberoylanilidehydroxamicacidsaharestorescardiomyocytecontractilityinaratmodelofearlydiabetes AT pramstallerpeterp thehistonedeacetylaseinhibitorsuberoylanilidehydroxamicacidsaharestorescardiomyocytecontractilityinaratmodelofearlydiabetes AT rossinialessandra thehistonedeacetylaseinhibitorsuberoylanilidehydroxamicacidsaharestorescardiomyocytecontractilityinaratmodelofearlydiabetes AT stillidonatella thehistonedeacetylaseinhibitorsuberoylanilidehydroxamicacidsaharestorescardiomyocytecontractilityinaratmodelofearlydiabetes AT bocchileonardo histonedeacetylaseinhibitorsuberoylanilidehydroxamicacidsaharestorescardiomyocytecontractilityinaratmodelofearlydiabetes AT mottabenedettam histonedeacetylaseinhibitorsuberoylanilidehydroxamicacidsaharestorescardiomyocytecontractilityinaratmodelofearlydiabetes AT savimonia histonedeacetylaseinhibitorsuberoylanilidehydroxamicacidsaharestorescardiomyocytecontractilityinaratmodelofearlydiabetes AT vilellarocchina histonedeacetylaseinhibitorsuberoylanilidehydroxamicacidsaharestorescardiomyocytecontractilityinaratmodelofearlydiabetes AT meravigliaviviana histonedeacetylaseinhibitorsuberoylanilidehydroxamicacidsaharestorescardiomyocytecontractilityinaratmodelofearlydiabetes AT rizzifederica histonedeacetylaseinhibitorsuberoylanilidehydroxamicacidsaharestorescardiomyocytecontractilityinaratmodelofearlydiabetes AT galatiserena histonedeacetylaseinhibitorsuberoylanilidehydroxamicacidsaharestorescardiomyocytecontractilityinaratmodelofearlydiabetes AT buschiniannamaria histonedeacetylaseinhibitorsuberoylanilidehydroxamicacidsaharestorescardiomyocytecontractilityinaratmodelofearlydiabetes AT lazzarettimirca histonedeacetylaseinhibitorsuberoylanilidehydroxamicacidsaharestorescardiomyocytecontractilityinaratmodelofearlydiabetes AT pramstallerpeterp histonedeacetylaseinhibitorsuberoylanilidehydroxamicacidsaharestorescardiomyocytecontractilityinaratmodelofearlydiabetes AT rossinialessandra histonedeacetylaseinhibitorsuberoylanilidehydroxamicacidsaharestorescardiomyocytecontractilityinaratmodelofearlydiabetes AT stillidonatella histonedeacetylaseinhibitorsuberoylanilidehydroxamicacidsaharestorescardiomyocytecontractilityinaratmodelofearlydiabetes |