Quantitative Proteomics Analysis Reveals That Cyclooxygenase-2 Modulates Mitochondrial Respiratory Chain Complex IV in Cardiomyocytes
- Autores
- Alvarez, Maria Soledad; Núñez, Estefanía; Fuertes Agudo, Marina; Cucarella, Carme; Fernandez Velasco, Maria; Boscá, Lisardo; Vázquez, Jesús; Rossignol, Rodrigue; Martin Sanz, Paloma; Casado, Marta
- Año de publicación
- 2022
- Idioma
- inglés
- Tipo de recurso
- artículo
- Estado
- versión publicada
- Descripción
- The biochemical mechanisms of cell injury and myocardial cell death after myocardial infarction remain unresolved. Cyclooxygenase 2 (COX-2), a key enzyme in prostanoid synthesis, is expressed in human ischemic myocardium and dilated cardiomyopathy, but it is absent in healthy hearts. To assess the role of COX-2 in cardiovascular physiopathology, we developed transgenic mice that constitutively express functional human COX-2 in cardiomyocytes under the control of the α-myosin heavy chain promoter. These animals had no apparent phenotype but were protected against ischemia-reperfusion injury in isolated hearts, with enhanced functional recovery and diminished cellular necrosis. To further explore the phenotype of this animal model, we carried out a differential proteome analysis of wild-type vs. transgenic cardiomyocytes. The results revealed a tissue-specific proteomic profile dominated by mitochondrial proteins. In particular, an increased expression of respiratory chain complex IV proteins was observed. This correlated with increased catalytic activity, enhanced respiratory capacity, and increased ATP levels in the heart of COX-2 transgenic mice. These data suggest a new link between COX-2 and mitochondria, which might contribute to the protective cardiac effects of COX-2 against ischemia-reperfusion injury.
Fil: Alvarez, Maria Soledad. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Medicina y Biología Experimental de Cuyo; Argentina
Fil: Núñez, Estefanía. No especifíca;
Fil: Fuertes Agudo, Marina. Consejo Superior de Investigaciones Científicas; España
Fil: Cucarella, Carme. Consejo Superior de Investigaciones Científicas; España
Fil: Fernandez Velasco, Maria. Consejo Superior de Investigaciones Científicas; España
Fil: Boscá, Lisardo. Consejo Superior de Investigaciones Científicas; España
Fil: Vázquez, Jesús. Consejo Superior de Investigaciones Científicas; España
Fil: Rossignol, Rodrigue. No especifíca;
Fil: Martin Sanz, Paloma. Consejo Superior de Investigaciones Científicas; España
Fil: Casado, Marta. Consejo Superior de Investigaciones Científicas; España - Materia
-
COX-2
MITOCHONDRIA
PROSTAGLANDINS
RESPIRATORY CAPACITY
TRANSGENIC ANIMALS - Nivel de accesibilidad
- acceso abierto
- Condiciones de uso
- https://creativecommons.org/licenses/by/2.5/ar/
- Repositorio
- Institución
- Consejo Nacional de Investigaciones Científicas y Técnicas
- OAI Identificador
- oai:ri.conicet.gov.ar:11336/217891
Ver los metadatos del registro completo
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oai:ri.conicet.gov.ar:11336/217891 |
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Quantitative Proteomics Analysis Reveals That Cyclooxygenase-2 Modulates Mitochondrial Respiratory Chain Complex IV in CardiomyocytesAlvarez, Maria SoledadNúñez, EstefaníaFuertes Agudo, MarinaCucarella, CarmeFernandez Velasco, MariaBoscá, LisardoVázquez, JesúsRossignol, RodrigueMartin Sanz, PalomaCasado, MartaCOX-2MITOCHONDRIAPROSTAGLANDINSRESPIRATORY CAPACITYTRANSGENIC ANIMALShttps://purl.org/becyt/ford/3.1https://purl.org/becyt/ford/3The biochemical mechanisms of cell injury and myocardial cell death after myocardial infarction remain unresolved. Cyclooxygenase 2 (COX-2), a key enzyme in prostanoid synthesis, is expressed in human ischemic myocardium and dilated cardiomyopathy, but it is absent in healthy hearts. To assess the role of COX-2 in cardiovascular physiopathology, we developed transgenic mice that constitutively express functional human COX-2 in cardiomyocytes under the control of the α-myosin heavy chain promoter. These animals had no apparent phenotype but were protected against ischemia-reperfusion injury in isolated hearts, with enhanced functional recovery and diminished cellular necrosis. To further explore the phenotype of this animal model, we carried out a differential proteome analysis of wild-type vs. transgenic cardiomyocytes. The results revealed a tissue-specific proteomic profile dominated by mitochondrial proteins. In particular, an increased expression of respiratory chain complex IV proteins was observed. This correlated with increased catalytic activity, enhanced respiratory capacity, and increased ATP levels in the heart of COX-2 transgenic mice. These data suggest a new link between COX-2 and mitochondria, which might contribute to the protective cardiac effects of COX-2 against ischemia-reperfusion injury.Fil: Alvarez, Maria Soledad. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Medicina y Biología Experimental de Cuyo; ArgentinaFil: Núñez, Estefanía. No especifíca;Fil: Fuertes Agudo, Marina. Consejo Superior de Investigaciones Científicas; EspañaFil: Cucarella, Carme. Consejo Superior de Investigaciones Científicas; EspañaFil: Fernandez Velasco, Maria. Consejo Superior de Investigaciones Científicas; EspañaFil: Boscá, Lisardo. Consejo Superior de Investigaciones Científicas; EspañaFil: Vázquez, Jesús. Consejo Superior de Investigaciones Científicas; EspañaFil: Rossignol, Rodrigue. No especifíca;Fil: Martin Sanz, Paloma. Consejo Superior de Investigaciones Científicas; EspañaFil: Casado, Marta. Consejo Superior de Investigaciones Científicas; EspañaMDPI2022-11info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/217891Alvarez, Maria Soledad; Núñez, Estefanía; Fuertes Agudo, Marina; Cucarella, Carme; Fernandez Velasco, Maria; et al.; Quantitative Proteomics Analysis Reveals That Cyclooxygenase-2 Modulates Mitochondrial Respiratory Chain Complex IV in Cardiomyocytes; MDPI; International Journal of Molecular Sciences; 23; 21; 11-2022; 1-191661-65961422-0067CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/doi/10.3390/ijms232113476info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-29T10:32:30Zoai:ri.conicet.gov.ar:11336/217891instacron:CONICETInstitucionalhttp://ri.conicet.gov.ar/Organismo científico-tecnológicoNo correspondehttp://ri.conicet.gov.ar/oai/requestdasensio@conicet.gov.ar; lcarlino@conicet.gov.arArgentinaNo correspondeNo correspondeNo correspondeopendoar:34982025-09-29 10:32:31.093CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse |
dc.title.none.fl_str_mv |
Quantitative Proteomics Analysis Reveals That Cyclooxygenase-2 Modulates Mitochondrial Respiratory Chain Complex IV in Cardiomyocytes |
title |
Quantitative Proteomics Analysis Reveals That Cyclooxygenase-2 Modulates Mitochondrial Respiratory Chain Complex IV in Cardiomyocytes |
spellingShingle |
Quantitative Proteomics Analysis Reveals That Cyclooxygenase-2 Modulates Mitochondrial Respiratory Chain Complex IV in Cardiomyocytes Alvarez, Maria Soledad COX-2 MITOCHONDRIA PROSTAGLANDINS RESPIRATORY CAPACITY TRANSGENIC ANIMALS |
title_short |
Quantitative Proteomics Analysis Reveals That Cyclooxygenase-2 Modulates Mitochondrial Respiratory Chain Complex IV in Cardiomyocytes |
title_full |
Quantitative Proteomics Analysis Reveals That Cyclooxygenase-2 Modulates Mitochondrial Respiratory Chain Complex IV in Cardiomyocytes |
title_fullStr |
Quantitative Proteomics Analysis Reveals That Cyclooxygenase-2 Modulates Mitochondrial Respiratory Chain Complex IV in Cardiomyocytes |
title_full_unstemmed |
Quantitative Proteomics Analysis Reveals That Cyclooxygenase-2 Modulates Mitochondrial Respiratory Chain Complex IV in Cardiomyocytes |
title_sort |
Quantitative Proteomics Analysis Reveals That Cyclooxygenase-2 Modulates Mitochondrial Respiratory Chain Complex IV in Cardiomyocytes |
dc.creator.none.fl_str_mv |
Alvarez, Maria Soledad Núñez, Estefanía Fuertes Agudo, Marina Cucarella, Carme Fernandez Velasco, Maria Boscá, Lisardo Vázquez, Jesús Rossignol, Rodrigue Martin Sanz, Paloma Casado, Marta |
author |
Alvarez, Maria Soledad |
author_facet |
Alvarez, Maria Soledad Núñez, Estefanía Fuertes Agudo, Marina Cucarella, Carme Fernandez Velasco, Maria Boscá, Lisardo Vázquez, Jesús Rossignol, Rodrigue Martin Sanz, Paloma Casado, Marta |
author_role |
author |
author2 |
Núñez, Estefanía Fuertes Agudo, Marina Cucarella, Carme Fernandez Velasco, Maria Boscá, Lisardo Vázquez, Jesús Rossignol, Rodrigue Martin Sanz, Paloma Casado, Marta |
author2_role |
author author author author author author author author author |
dc.subject.none.fl_str_mv |
COX-2 MITOCHONDRIA PROSTAGLANDINS RESPIRATORY CAPACITY TRANSGENIC ANIMALS |
topic |
COX-2 MITOCHONDRIA PROSTAGLANDINS RESPIRATORY CAPACITY TRANSGENIC ANIMALS |
purl_subject.fl_str_mv |
https://purl.org/becyt/ford/3.1 https://purl.org/becyt/ford/3 |
dc.description.none.fl_txt_mv |
The biochemical mechanisms of cell injury and myocardial cell death after myocardial infarction remain unresolved. Cyclooxygenase 2 (COX-2), a key enzyme in prostanoid synthesis, is expressed in human ischemic myocardium and dilated cardiomyopathy, but it is absent in healthy hearts. To assess the role of COX-2 in cardiovascular physiopathology, we developed transgenic mice that constitutively express functional human COX-2 in cardiomyocytes under the control of the α-myosin heavy chain promoter. These animals had no apparent phenotype but were protected against ischemia-reperfusion injury in isolated hearts, with enhanced functional recovery and diminished cellular necrosis. To further explore the phenotype of this animal model, we carried out a differential proteome analysis of wild-type vs. transgenic cardiomyocytes. The results revealed a tissue-specific proteomic profile dominated by mitochondrial proteins. In particular, an increased expression of respiratory chain complex IV proteins was observed. This correlated with increased catalytic activity, enhanced respiratory capacity, and increased ATP levels in the heart of COX-2 transgenic mice. These data suggest a new link between COX-2 and mitochondria, which might contribute to the protective cardiac effects of COX-2 against ischemia-reperfusion injury. Fil: Alvarez, Maria Soledad. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Medicina y Biología Experimental de Cuyo; Argentina Fil: Núñez, Estefanía. No especifíca; Fil: Fuertes Agudo, Marina. Consejo Superior de Investigaciones Científicas; España Fil: Cucarella, Carme. Consejo Superior de Investigaciones Científicas; España Fil: Fernandez Velasco, Maria. Consejo Superior de Investigaciones Científicas; España Fil: Boscá, Lisardo. Consejo Superior de Investigaciones Científicas; España Fil: Vázquez, Jesús. Consejo Superior de Investigaciones Científicas; España Fil: Rossignol, Rodrigue. No especifíca; Fil: Martin Sanz, Paloma. Consejo Superior de Investigaciones Científicas; España Fil: Casado, Marta. Consejo Superior de Investigaciones Científicas; España |
description |
The biochemical mechanisms of cell injury and myocardial cell death after myocardial infarction remain unresolved. Cyclooxygenase 2 (COX-2), a key enzyme in prostanoid synthesis, is expressed in human ischemic myocardium and dilated cardiomyopathy, but it is absent in healthy hearts. To assess the role of COX-2 in cardiovascular physiopathology, we developed transgenic mice that constitutively express functional human COX-2 in cardiomyocytes under the control of the α-myosin heavy chain promoter. These animals had no apparent phenotype but were protected against ischemia-reperfusion injury in isolated hearts, with enhanced functional recovery and diminished cellular necrosis. To further explore the phenotype of this animal model, we carried out a differential proteome analysis of wild-type vs. transgenic cardiomyocytes. The results revealed a tissue-specific proteomic profile dominated by mitochondrial proteins. In particular, an increased expression of respiratory chain complex IV proteins was observed. This correlated with increased catalytic activity, enhanced respiratory capacity, and increased ATP levels in the heart of COX-2 transgenic mice. These data suggest a new link between COX-2 and mitochondria, which might contribute to the protective cardiac effects of COX-2 against ischemia-reperfusion injury. |
publishDate |
2022 |
dc.date.none.fl_str_mv |
2022-11 |
dc.type.none.fl_str_mv |
info:eu-repo/semantics/article info:eu-repo/semantics/publishedVersion http://purl.org/coar/resource_type/c_6501 info:ar-repo/semantics/articulo |
format |
article |
status_str |
publishedVersion |
dc.identifier.none.fl_str_mv |
http://hdl.handle.net/11336/217891 Alvarez, Maria Soledad; Núñez, Estefanía; Fuertes Agudo, Marina; Cucarella, Carme; Fernandez Velasco, Maria; et al.; Quantitative Proteomics Analysis Reveals That Cyclooxygenase-2 Modulates Mitochondrial Respiratory Chain Complex IV in Cardiomyocytes; MDPI; International Journal of Molecular Sciences; 23; 21; 11-2022; 1-19 1661-6596 1422-0067 CONICET Digital CONICET |
url |
http://hdl.handle.net/11336/217891 |
identifier_str_mv |
Alvarez, Maria Soledad; Núñez, Estefanía; Fuertes Agudo, Marina; Cucarella, Carme; Fernandez Velasco, Maria; et al.; Quantitative Proteomics Analysis Reveals That Cyclooxygenase-2 Modulates Mitochondrial Respiratory Chain Complex IV in Cardiomyocytes; MDPI; International Journal of Molecular Sciences; 23; 21; 11-2022; 1-19 1661-6596 1422-0067 CONICET Digital CONICET |
dc.language.none.fl_str_mv |
eng |
language |
eng |
dc.relation.none.fl_str_mv |
info:eu-repo/semantics/altIdentifier/doi/10.3390/ijms232113476 |
dc.rights.none.fl_str_mv |
info:eu-repo/semantics/openAccess https://creativecommons.org/licenses/by/2.5/ar/ |
eu_rights_str_mv |
openAccess |
rights_invalid_str_mv |
https://creativecommons.org/licenses/by/2.5/ar/ |
dc.format.none.fl_str_mv |
application/pdf application/pdf |
dc.publisher.none.fl_str_mv |
MDPI |
publisher.none.fl_str_mv |
MDPI |
dc.source.none.fl_str_mv |
reponame:CONICET Digital (CONICET) instname:Consejo Nacional de Investigaciones Científicas y Técnicas |
reponame_str |
CONICET Digital (CONICET) |
collection |
CONICET Digital (CONICET) |
instname_str |
Consejo Nacional de Investigaciones Científicas y Técnicas |
repository.name.fl_str_mv |
CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicas |
repository.mail.fl_str_mv |
dasensio@conicet.gov.ar; lcarlino@conicet.gov.ar |
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1844614338469429248 |
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13.070432 |