Quantitative Proteomics Analysis Reveals That Cyclooxygenase-2 Modulates Mitochondrial Respiratory Chain Complex IV in Cardiomyocytes

Alvarez, Maria Soledad; Núñez, Estefanía; Fuertes-Agudo, Marina; Cucarella, Carme; Fernandez-Velasco, Maria; Boscá, Lisardo; Vázquez, Jesús; Rossignol, Rodrigue; Martin-Sanz, Paloma; Casado, Marta

doi:10.3390/ijms232113476

Open AccessArticle

Quantitative Proteomics Analysis Reveals That Cyclooxygenase-2 Modulates Mitochondrial Respiratory Chain Complex IV in Cardiomyocytes

by

Maria Soledad Alvarez

^1,†,‡

,

Estefanía Núñez

^2,3,†,

Marina Fuertes-Agudo

^1,4

,

Carme Cucarella

^1,4,

Maria Fernandez-Velasco

^3,5

,

Lisardo Boscá

^3,6

,

Jesús Vázquez

^2,3,

Rodrigue Rossignol

⁷,

Paloma Martin-Sanz

^4,6 and

Marta Casado

^1,4,*

¹

Instituto de Biomedicina de Valencia (IBV), CSIC, Jaume Roig 11, 46010 Valencia, Spain

²

Laboratory of Cardiovascular Proteomics, Centro Nacional de Investigaciones Cardiovasculares (CNIC), Melchor Fernández Almagro, 3, 28029 Madrid, Spain

³

CIBER de Enfermedades Cardiovasculares (CIBERCV), Monforte de Lemos 3-5, 28029 Madrid, Spain

⁴

Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Monforte de Lemos 3-5, 28029 Madrid, Spain

⁵

Instituto de Investigación Hospital Universitario La Paz, IDIPAZ, Paseo de la Castellana 261, 28046 Madrid, Spain

⁶

Instituto de Investigaciones Biomedicas Alberto Sols (IIBM), CSIC-UAM, Arturo Duperier 4, 28029 Madrid, Spain

⁷

Laboratoire Maladies Rares, CHU Pellegrin Place Amelie Rab, 33076 Bordeaux, France

^*

Author to whom correspondence should be addressed.

^†

These authors contributed equally to this work.

^‡

Current Address: Instituto de Medicina y Biología Experimental de Cuyo (IMBECU), CONICET, Laboratorio de Biología Vascular, Facultad de Ciencias Médicas-UNCuyo, Centro Universitario, Mendoza 5500, Argentina.

Int. J. Mol. Sci. 2022, 23(21), 13476; https://doi.org/10.3390/ijms232113476

Submission received: 3 October 2022 / Revised: 24 October 2022 / Accepted: 30 October 2022 / Published: 3 November 2022

(This article belongs to the Special Issue Mitochondria at the Heart of Metabolic Disorders)

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Abstract

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.

Keywords: COX-2; prostaglandins; mitochondria; respiratory capacity; transgenic animals

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MDPI and ACS Style

Alvarez, M.S.; Núñez, E.; Fuertes-Agudo, M.; Cucarella, C.; Fernandez-Velasco, M.; Boscá, L.; Vázquez, J.; Rossignol, R.; Martin-Sanz, P.; Casado, M. Quantitative Proteomics Analysis Reveals That Cyclooxygenase-2 Modulates Mitochondrial Respiratory Chain Complex IV in Cardiomyocytes. Int. J. Mol. Sci. 2022, 23, 13476. https://doi.org/10.3390/ijms232113476

AMA Style

Alvarez MS, Núñez E, Fuertes-Agudo M, Cucarella C, Fernandez-Velasco M, Boscá L, Vázquez J, Rossignol R, Martin-Sanz P, Casado M. Quantitative Proteomics Analysis Reveals That Cyclooxygenase-2 Modulates Mitochondrial Respiratory Chain Complex IV in Cardiomyocytes. International Journal of Molecular Sciences. 2022; 23(21):13476. https://doi.org/10.3390/ijms232113476

Chicago/Turabian Style

Alvarez, Maria Soledad, Estefanía Núñez, Marina Fuertes-Agudo, Carme Cucarella, Maria Fernandez-Velasco, Lisardo Boscá, Jesús Vázquez, Rodrigue Rossignol, Paloma Martin-Sanz, and Marta Casado. 2022. "Quantitative Proteomics Analysis Reveals That Cyclooxygenase-2 Modulates Mitochondrial Respiratory Chain Complex IV in Cardiomyocytes" International Journal of Molecular Sciences 23, no. 21: 13476. https://doi.org/10.3390/ijms232113476

APA Style

Alvarez, M. S., Núñez, E., Fuertes-Agudo, M., Cucarella, C., Fernandez-Velasco, M., Boscá, L., Vázquez, J., Rossignol, R., Martin-Sanz, P., & Casado, M. (2022). Quantitative Proteomics Analysis Reveals That Cyclooxygenase-2 Modulates Mitochondrial Respiratory Chain Complex IV in Cardiomyocytes. International Journal of Molecular Sciences, 23(21), 13476. https://doi.org/10.3390/ijms232113476

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Quantitative Proteomics Analysis Reveals That Cyclooxygenase-2 Modulates Mitochondrial Respiratory Chain Complex IV in Cardiomyocytes

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