Oxidative Post-translational Protein Modifications upon Ischemia/Reperfusion Injury

While reperfusion, or restoration of coronary blood flow in acute myocardial infarction, is a requisite for myocardial salvage, it can paradoxically induce a specific damage known as ischemia/reperfusion (I/R) injury. Our understanding of the precise pathophysiological molecular alterations leading...

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Authors: Binek, Aleksandra, Castans, Celia, Jorge, Inmaculada, Bagwan, Navratan, Rodríguez, José Manuel, Fernández-Jiménez, Rodrigo, Galán-Arriola, Carlos, Oliver, Eduardo, Gómez, Mónica, Clemente-Moragón, Agustín, Ibáñez, Borja, Camafeita, Emilio, Vázquez, Jesús
Format: article
Status:Published version
Publication Date:2024
Country:España
Institution:Consejo Superior de Investigaciones Científicas (CSIC)
Repository:DIGITAL.CSIC. Repositorio Institucional del CSIC
OAI Identifier:oai:digital.csic.es:10261/356313
Online Access:http://hdl.handle.net/10261/356313
Access Level:Open access
Keyword:Myocardial infarction
Ischemia/reperfusion
Ischemic preconditioning
Pig ischemia/reperfusion model
Proteomics
Post-translational modifications
Oxidative post-translational modifications
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dc.title.none.fl_str_mv Oxidative Post-translational Protein Modifications upon Ischemia/Reperfusion Injury
title Oxidative Post-translational Protein Modifications upon Ischemia/Reperfusion Injury
spellingShingle Oxidative Post-translational Protein Modifications upon Ischemia/Reperfusion Injury
Binek, Aleksandra
Myocardial infarction
Ischemia/reperfusion
Ischemic preconditioning
Pig ischemia/reperfusion model
Proteomics
Post-translational modifications
Oxidative post-translational modifications
title_short Oxidative Post-translational Protein Modifications upon Ischemia/Reperfusion Injury
title_full Oxidative Post-translational Protein Modifications upon Ischemia/Reperfusion Injury
title_fullStr Oxidative Post-translational Protein Modifications upon Ischemia/Reperfusion Injury
title_full_unstemmed Oxidative Post-translational Protein Modifications upon Ischemia/Reperfusion Injury
title_sort Oxidative Post-translational Protein Modifications upon Ischemia/Reperfusion Injury
dc.creator.none.fl_str_mv Binek, Aleksandra
Castans, Celia
Jorge, Inmaculada
Bagwan, Navratan
Rodríguez, José Manuel
Fernández-Jiménez, Rodrigo
Galán-Arriola, Carlos
Oliver, Eduardo
Gómez, Mónica
Clemente-Moragón, Agustín
Ibáñez, Borja
Camafeita, Emilio
Vázquez, Jesús
author Binek, Aleksandra
author_facet Binek, Aleksandra
Castans, Celia
Jorge, Inmaculada
Bagwan, Navratan
Rodríguez, José Manuel
Fernández-Jiménez, Rodrigo
Galán-Arriola, Carlos
Oliver, Eduardo
Gómez, Mónica
Clemente-Moragón, Agustín
Ibáñez, Borja
Camafeita, Emilio
Vázquez, Jesús
author_role author
author2 Castans, Celia
Jorge, Inmaculada
Bagwan, Navratan
Rodríguez, José Manuel
Fernández-Jiménez, Rodrigo
Galán-Arriola, Carlos
Oliver, Eduardo
Gómez, Mónica
Clemente-Moragón, Agustín
Ibáñez, Borja
Camafeita, Emilio
Vázquez, Jesús
author2_role author
author
author
author
author
author
author
author
author
author
author
author
dc.contributor.none.fl_str_mv Ministerio de Ciencia, Innovación y Universidades (España)
Ministerio de Ciencia e Innovación (España)
Agencia Estatal de Investigación (España)
European Commission
Comunidad de Madrid
Fundación la Caixa
Instituto de Salud Carlos III
Consejo Superior de Investigaciones Científicas [https://ror.org/02gfc7t72]
dc.subject.none.fl_str_mv Myocardial infarction
Ischemia/reperfusion
Ischemic preconditioning
Pig ischemia/reperfusion model
Proteomics
Post-translational modifications
Oxidative post-translational modifications
topic Myocardial infarction
Ischemia/reperfusion
Ischemic preconditioning
Pig ischemia/reperfusion model
Proteomics
Post-translational modifications
Oxidative post-translational modifications
description While reperfusion, or restoration of coronary blood flow in acute myocardial infarction, is a requisite for myocardial salvage, it can paradoxically induce a specific damage known as ischemia/reperfusion (I/R) injury. Our understanding of the precise pathophysiological molecular alterations leading to I/R remains limited. In this study, we conducted a comprehensive and unbiased time-course analysis of post-translational modifications (PTMs) in the post-reperfused myocardium of two different animal models (pig and mouse) and evaluated the effect of two different cardioprotective therapies (ischemic preconditioning and neutrophil depletion). In pigs, a first wave of irreversible oxidative damage was observed at the earliest reperfusion time (20 min), impacting proteins essential for cardiac contraction. A second wave, characterized by irreversible oxidation on different residues and reversible Cys oxidation, occurred at late stages (6–12 h), affecting mitochondrial, sarcomere, and inflammation-related proteins. Ischemic preconditioning mitigated the I/R damage caused by the late oxidative wave. In the mouse model, the two-phase pattern of oxidative damage was replicated, and neutrophil depletion mitigated the late wave of I/R-related damage by preventing both Cys reversible oxidation and irreversible oxidation. Altogether, these data identify protein PTMs occurring late after reperfusion as an actionable therapeutic target to reduce the impact of I/R injury.
publishDate 2024
dc.date.none.fl_str_mv 2024
2024
2024
dc.type.none.fl_str_mv info:eu-repo/semantics/article
http://purl.org/coar/resource_type/c_6501
Publisher's version
info:eu-repo/semantics/publishedVersion
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dc.identifier.none.fl_str_mv http://hdl.handle.net/10261/356313
url http://hdl.handle.net/10261/356313
dc.language.none.fl_str_mv Inglés
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dc.publisher.none.fl_str_mv Multidisciplinary Digital Publishing Institute
publisher.none.fl_str_mv Multidisciplinary Digital Publishing Institute
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instname:Consejo Superior de Investigaciones Científicas (CSIC)
instname_str Consejo Superior de Investigaciones Científicas (CSIC)
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spelling Oxidative Post-translational Protein Modifications upon Ischemia/Reperfusion InjuryBinek, AleksandraCastans, CeliaJorge, InmaculadaBagwan, NavratanRodríguez, José ManuelFernández-Jiménez, RodrigoGalán-Arriola, CarlosOliver, EduardoGómez, MónicaClemente-Moragón, AgustínIbáñez, BorjaCamafeita, EmilioVázquez, JesúsMyocardial infarctionIschemia/reperfusionIschemic preconditioningPig ischemia/reperfusion modelProteomicsPost-translational modificationsOxidative post-translational modificationsWhile reperfusion, or restoration of coronary blood flow in acute myocardial infarction, is a requisite for myocardial salvage, it can paradoxically induce a specific damage known as ischemia/reperfusion (I/R) injury. Our understanding of the precise pathophysiological molecular alterations leading to I/R remains limited. In this study, we conducted a comprehensive and unbiased time-course analysis of post-translational modifications (PTMs) in the post-reperfused myocardium of two different animal models (pig and mouse) and evaluated the effect of two different cardioprotective therapies (ischemic preconditioning and neutrophil depletion). In pigs, a first wave of irreversible oxidative damage was observed at the earliest reperfusion time (20 min), impacting proteins essential for cardiac contraction. A second wave, characterized by irreversible oxidation on different residues and reversible Cys oxidation, occurred at late stages (6–12 h), affecting mitochondrial, sarcomere, and inflammation-related proteins. Ischemic preconditioning mitigated the I/R damage caused by the late oxidative wave. In the mouse model, the two-phase pattern of oxidative damage was replicated, and neutrophil depletion mitigated the late wave of I/R-related damage by preventing both Cys reversible oxidation and irreversible oxidation. Altogether, these data identify protein PTMs occurring late after reperfusion as an actionable therapeutic target to reduce the impact of I/R injury.This study was supported by competitive grants from the MCIN/AEI/10.13039/501100011033/ and FEDER Una manera de hacer Europa (PID2021-122348NB-I00 and PID2022-140176OB-I00), the MCIN/AEI/10.13039/501100011033 the Unión Europea NextGenerationEU/PRTR (PLEC2022-009235, and PLEC2022-009298), the Comunidad de Madrid (Programa S2022/BDM-7333-CM, INMUNO-VAR, P2022/BMD-7333, and RENIM-CM, P2022/BMD-7403), “la Caixa” Banking Foundation (HR17-00247, LCF/PR/HP22/52320018, and LCF/PR/HR22/52420019), and the European Commission (ERC Consolidator Grant “MATRIX”, 819775). Rodrigo Fernandez-Jimenez is the recipient of grant PI22/01560 funded by the ISCIII-Fondo de Investigación Sanitaria and co-funded by the European Union. Aleksandra Binek and Navratan Bagwan were FP7-PEOPLE-2013-ITN-Cardionext fellows from the European Union’s Seventh Framework Programme (Marie Curie Actions). Celia Castans holds a Formación del Profesorado Universitario (FPU14/05292) fellowship from the Spanish Ministry of Education, Culture and Sports. Eduardo Oliver holds a Ramón y Cajal fellowship (RYC2020-028884-I) and granted by the MCIN/AEI/10.13039/501100011033/ and FEDER Una manera de hacer Europa (PID2021-133167OB-100) and by “ESF Investing in your future”. The CNIC is supported by the Instituto de Salud Carlos III (ISCIII), the Ministerio de Ciencia e Innovación (MCIN), and the Pro CNIC Foundation and is a Severo Ochoa Center of Excellence (grant CEX2020-001041-S funded by MICIN/AEI/10.13039/501100011033).With funding from the Spanish government through the ‘Severo Ochoa Centre of Excellence’ accreditation (CEX2020-001041-S).Peer reviewedMultidisciplinary Digital Publishing InstituteMinisterio de Ciencia, Innovación y Universidades (España)Ministerio de Ciencia e Innovación (España)Agencia Estatal de Investigación (España)European CommissionComunidad de MadridFundación la CaixaInstituto de Salud Carlos IIIConsejo Superior de Investigaciones Científicas [https://ror.org/02gfc7t72]202420242024info:eu-repo/semantics/articlehttp://purl.org/coar/resource_type/c_6501Publisher's versioninfo:eu-repo/semantics/publishedVersionapplication/pdfhttp://hdl.handle.net/10261/356313reponame:DIGITAL.CSIC. Repositorio Institucional del CSICinstname:Consejo Superior de Investigaciones Científicas (CSIC)Inglés#PLACEHOLDER_PARENT_METADATA_VALUE##PLACEHOLDER_PARENT_METADATA_VALUE##PLACEHOLDER_PARENT_METADATA_VALUE##PLACEHOLDER_PARENT_METADATA_VALUE##PLACEHOLDER_PARENT_METADATA_VALUE##PLACEHOLDER_PARENT_METADATA_VALUE#info:eu-repo/grantAgreement/AEI/Plan Estatal de Investigación Científica y Técnica y de Innovación 2021-2023/PID2021-122348NB-I00info:eu-repo/grantAgreement/AEI/Plan Estatal de Investigación Científica y Técnica y de Innovación 2021-2023/PID2022-140176OB-I00S2022/BDM-7333-CM/INMUNO-VARP2022/BMD-7333/RENIM-CMinfo:eu-repo/grantAgreement/AEI//RYC2020-028884-Iinfo:eu-repo/grantAgreement/AEI/Plan Estatal de Investigación Científica y Técnica y de Innovación 2021-2023/CEX2020-001041-Shttps://doi.org/10.3390/antiox13010106Síinfo:eu-repo/semantics/openAccessoai:digital.csic.es:10261/3563132026-05-22T06:33:51Z
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