Cargando…

ATP synthase subunit alpha and LV mass in ischaemic human hearts

Mitochondrial dysfunction plays a critical role in the development of ischaemic cardiomyopathy (ICM). In this study, the mitochondrial proteome in the cardiac tissue of ICM patients was analysed by quantitative differential electrophoresis (2D-DIGE) and mass spectrometry (MS) for the first time to p...

Descripción completa

Detalles Bibliográficos
Autores principales: Roselló-Lletí, Esther, Tarazón, Estefanía, Barderas, María G, Ortega, Ana, Molina-Navarro, Maria Micaela, Martínez, Alba, Lago, Francisca, Martínez-Dolz, Luis, González-Juanatey, Jose Ramón, Salvador, Antonio, Portolés, Manuel, Rivera, Miguel
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BlackWell Publishing Ltd 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4407605/
https://www.ncbi.nlm.nih.gov/pubmed/25382018
http://dx.doi.org/10.1111/jcmm.12477
_version_ 1782367938585559040
author Roselló-Lletí, Esther
Tarazón, Estefanía
Barderas, María G
Ortega, Ana
Molina-Navarro, Maria Micaela
Martínez, Alba
Lago, Francisca
Martínez-Dolz, Luis
González-Juanatey, Jose Ramón
Salvador, Antonio
Portolés, Manuel
Rivera, Miguel
author_facet Roselló-Lletí, Esther
Tarazón, Estefanía
Barderas, María G
Ortega, Ana
Molina-Navarro, Maria Micaela
Martínez, Alba
Lago, Francisca
Martínez-Dolz, Luis
González-Juanatey, Jose Ramón
Salvador, Antonio
Portolés, Manuel
Rivera, Miguel
author_sort Roselló-Lletí, Esther
collection PubMed
description Mitochondrial dysfunction plays a critical role in the development of ischaemic cardiomyopathy (ICM). In this study, the mitochondrial proteome in the cardiac tissue of ICM patients was analysed by quantitative differential electrophoresis (2D-DIGE) and mass spectrometry (MS) for the first time to provide new insights into cardiac dysfunction in this cardiomyopathy. We isolated mitochondria from LV samples of explanted hearts of ICM patients (n = 8) and control donors (n = 8) and used a proteomic approach to investigate the variations in mitochondrial protein expression. We found that most of the altered proteins were involved in cardiac energy metabolism (82%). We focused on ATPA, which is involved in energy production, and dihydrolipoyl dehydrogenase, implicated in substrate utilization, and observed that these molecules were overexpressed and that the changes detected in the processes mediated by these proteins were closely related. Notably, we found that ATPA overexpression was associated with reduction in LV mass (r = −0.74, P < 0.01). We also found a substantial increase in the expression of elongation factor Tu, a molecule implicated in protein synthesis, and PRDX3, involved in the stress response. All of these changes were validated using classical techniques and by using novel and precise selected reaction monitoring analysis and an RNA sequencing approach, with the total heart samples being increased to 24. This study provides key insights that enhance our understanding of the cellular mechanisms related to the pathophysiology of ICM and could lead to the development of aetiology-specific heart failure therapies. ATPA could serve as a molecular target suitable for new therapeutic interventions.
format Online
Article
Text
id pubmed-4407605
institution National Center for Biotechnology Information
language English
publishDate 2015
publisher BlackWell Publishing Ltd
record_format MEDLINE/PubMed
spelling pubmed-44076052015-04-23 ATP synthase subunit alpha and LV mass in ischaemic human hearts Roselló-Lletí, Esther Tarazón, Estefanía Barderas, María G Ortega, Ana Molina-Navarro, Maria Micaela Martínez, Alba Lago, Francisca Martínez-Dolz, Luis González-Juanatey, Jose Ramón Salvador, Antonio Portolés, Manuel Rivera, Miguel J Cell Mol Med Original Articles Mitochondrial dysfunction plays a critical role in the development of ischaemic cardiomyopathy (ICM). In this study, the mitochondrial proteome in the cardiac tissue of ICM patients was analysed by quantitative differential electrophoresis (2D-DIGE) and mass spectrometry (MS) for the first time to provide new insights into cardiac dysfunction in this cardiomyopathy. We isolated mitochondria from LV samples of explanted hearts of ICM patients (n = 8) and control donors (n = 8) and used a proteomic approach to investigate the variations in mitochondrial protein expression. We found that most of the altered proteins were involved in cardiac energy metabolism (82%). We focused on ATPA, which is involved in energy production, and dihydrolipoyl dehydrogenase, implicated in substrate utilization, and observed that these molecules were overexpressed and that the changes detected in the processes mediated by these proteins were closely related. Notably, we found that ATPA overexpression was associated with reduction in LV mass (r = −0.74, P < 0.01). We also found a substantial increase in the expression of elongation factor Tu, a molecule implicated in protein synthesis, and PRDX3, involved in the stress response. All of these changes were validated using classical techniques and by using novel and precise selected reaction monitoring analysis and an RNA sequencing approach, with the total heart samples being increased to 24. This study provides key insights that enhance our understanding of the cellular mechanisms related to the pathophysiology of ICM and could lead to the development of aetiology-specific heart failure therapies. ATPA could serve as a molecular target suitable for new therapeutic interventions. BlackWell Publishing Ltd 2015-02 2014-11-09 /pmc/articles/PMC4407605/ /pubmed/25382018 http://dx.doi.org/10.1111/jcmm.12477 Text en © 2014 The Authors. Journal of Cellular and Molecular Medicine published by John Wiley & Sons Ltd and Foundation for Cellular and Molecular Medicine. http://creativecommons.org/licenses/by/4.0/ This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
spellingShingle Original Articles
Roselló-Lletí, Esther
Tarazón, Estefanía
Barderas, María G
Ortega, Ana
Molina-Navarro, Maria Micaela
Martínez, Alba
Lago, Francisca
Martínez-Dolz, Luis
González-Juanatey, Jose Ramón
Salvador, Antonio
Portolés, Manuel
Rivera, Miguel
ATP synthase subunit alpha and LV mass in ischaemic human hearts
title ATP synthase subunit alpha and LV mass in ischaemic human hearts
title_full ATP synthase subunit alpha and LV mass in ischaemic human hearts
title_fullStr ATP synthase subunit alpha and LV mass in ischaemic human hearts
title_full_unstemmed ATP synthase subunit alpha and LV mass in ischaemic human hearts
title_short ATP synthase subunit alpha and LV mass in ischaemic human hearts
title_sort atp synthase subunit alpha and lv mass in ischaemic human hearts
topic Original Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4407605/
https://www.ncbi.nlm.nih.gov/pubmed/25382018
http://dx.doi.org/10.1111/jcmm.12477
work_keys_str_mv AT rosellolletiesther atpsynthasesubunitalphaandlvmassinischaemichumanhearts
AT tarazonestefania atpsynthasesubunitalphaandlvmassinischaemichumanhearts
AT barderasmariag atpsynthasesubunitalphaandlvmassinischaemichumanhearts
AT ortegaana atpsynthasesubunitalphaandlvmassinischaemichumanhearts
AT molinanavarromariamicaela atpsynthasesubunitalphaandlvmassinischaemichumanhearts
AT martinezalba atpsynthasesubunitalphaandlvmassinischaemichumanhearts
AT lagofrancisca atpsynthasesubunitalphaandlvmassinischaemichumanhearts
AT martinezdolzluis atpsynthasesubunitalphaandlvmassinischaemichumanhearts
AT gonzalezjuanateyjoseramon atpsynthasesubunitalphaandlvmassinischaemichumanhearts
AT salvadorantonio atpsynthasesubunitalphaandlvmassinischaemichumanhearts
AT portolesmanuel atpsynthasesubunitalphaandlvmassinischaemichumanhearts
AT riveramiguel atpsynthasesubunitalphaandlvmassinischaemichumanhearts