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
CONICET Digital (CONICET)
Institución
Consejo Nacional de Investigaciones Científicas y Técnicas
OAI Identificador
oai:ri.conicet.gov.ar:11336/217891
Acceder
id CONICETDig_7cb612acfead4d479bc6b64cf3d9263f
oai_identifier_str oai:ri.conicet.gov.ar:11336/217891
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling 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 Técnicas2025-10-22T12:04:53Zoai: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:34982025-10-22 12:04:53.509CONICET 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
_version_ 1846782400111050752
score 12.982451

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