Energy substrate metabolism, mitochondrial structure and oxidative stress after cardiac ischemia-reperfusion in mice lacking UCP3
Myocardial ischemia-reperfusion (IR) injury may result in cardiomyocyte dysfunction. Mitochondria play a critical role in cardiomyocyte recovery after IR injury. The mitochondrial uncoupling protein 3 (UCP3) has been proposed to reduce mitochondrial reactive oxygen species (ROS) production and to fa...
| Autores: | , , , , , , , , , , , , , |
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| Tipo de recurso: | artículo |
| Estado: | Versión publicada |
| Fecha de publicación: | 2023 |
| País: | España |
| Institución: | Consejo Superior de Investigaciones Científicas (CSIC) |
| Repositorio: | DIGITAL.CSIC. Repositorio Institucional del CSIC |
| OAI Identifier: | oai:digital.csic.es:10261/347026 |
| Acceso en línea: | http://hdl.handle.net/10261/347026 |
| Access Level: | acceso abierto |
| Palabra clave: | Energy metabolism Ischemia-reperfusion injury Mitochondrial respiration Mitochondrial structure Oxidative stress UCP3 (uncoupling protein 3) |
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Energy substrate metabolism, mitochondrial structure and oxidative stress after cardiac ischemia-reperfusion in mice lacking UCP3Sánchez-Pérez, PatriciaMata, Ana M.Torp, May-KristinLópez-Bernardo, EliaHeiestad, Christina MAronsen, Jan MagnusMolina-Iracheta, AntonioJiménez-Borreguero, Luis JGarcía-Roves, PabloCosta, Ana S HFrezza, ChristianMurphy, Michael PStenslokken, Kåre-OlavCadenas, SusanaEnergy metabolismIschemia-reperfusion injuryMitochondrial respirationMitochondrial structureOxidative stressUCP3 (uncoupling protein 3)Myocardial ischemia-reperfusion (IR) injury may result in cardiomyocyte dysfunction. Mitochondria play a critical role in cardiomyocyte recovery after IR injury. The mitochondrial uncoupling protein 3 (UCP3) has been proposed to reduce mitochondrial reactive oxygen species (ROS) production and to facilitate fatty acid oxidation. As both mechanisms might be protective following IR injury, we investigated functional, mitochondrial structural, and metabolic cardiac remodeling in wild-type mice and in mice lacking UCP3 (UCP3–KO) after IR. Results showed that infarct size in isolated perfused hearts subjected to IR ex vivo was larger in adult and old UCP3–KO mice than in equivalent wild-type mice, and was accompanied by higher levels of creatine kinase in the effluent and by more pronounced mitochondrial structural changes. The greater myocardial damage in UCP3–KO hearts was confirmed in vivo after coronary artery occlusion followed by reperfusion. S1QEL, a suppressor of superoxide generation from site I in complex I, limited infarct size in UCP3–KO hearts, pointing to exacerbated superoxide production as a possible cause of the damage. Metabolomics analysis of isolated perfused hearts confirmed the reported accumulation of succinate, xanthine and hypoxanthine during ischemia, and a shift to anaerobic glucose utilization, which all recovered upon reoxygenation. The metabolic response to ischemia and IR was similar in UCP3–KO and wild-type hearts, being lipid and energy metabolism the most affected pathways. Fatty acid oxidation and complex I (but not complex II) activity were equally impaired after IR. Overall, our results indicate that UCP3 deficiency promotes enhanced superoxide generation and mitochondrial structural changes that increase the vulnerability of the myocardium to IR injury.The work in our laboratory is funded the Instituto de Salud Carlos III (FIS PI19/01030) to SC. Institutional grants from the Fundación Ramón Areces and Banco de Santander to the CBMSO are also acknowledged.Peer reviewedInstituto de Salud Carlos IIIFundación Ramón ArecesBanco SantanderConsejo Superior de Investigaciones Científicas [https://ror.org/02gfc7t72]2024202420232024info:eu-repo/semantics/articlehttp://purl.org/coar/resource_type/c_6501Publisher's versioninfo:eu-repo/semantics/publishedVersionhttp://hdl.handle.net/10261/347026reponame:DIGITAL.CSIC. Repositorio Institucional del CSICinstname:Consejo Superior de Investigaciones Científicas (CSIC)Ingléshttp://dx.doi.org/10.1016/j.freeradbiomed.2023.05.014Síinfo:eu-repo/semantics/openAccessoai:digital.csic.es:10261/3470262026-05-22T06:33:51Z |
| dc.title.none.fl_str_mv |
Energy substrate metabolism, mitochondrial structure and oxidative stress after cardiac ischemia-reperfusion in mice lacking UCP3 |
| title |
Energy substrate metabolism, mitochondrial structure and oxidative stress after cardiac ischemia-reperfusion in mice lacking UCP3 |
| spellingShingle |
Energy substrate metabolism, mitochondrial structure and oxidative stress after cardiac ischemia-reperfusion in mice lacking UCP3 Sánchez-Pérez, Patricia Energy metabolism Ischemia-reperfusion injury Mitochondrial respiration Mitochondrial structure Oxidative stress UCP3 (uncoupling protein 3) |
| title_short |
Energy substrate metabolism, mitochondrial structure and oxidative stress after cardiac ischemia-reperfusion in mice lacking UCP3 |
| title_full |
Energy substrate metabolism, mitochondrial structure and oxidative stress after cardiac ischemia-reperfusion in mice lacking UCP3 |
| title_fullStr |
Energy substrate metabolism, mitochondrial structure and oxidative stress after cardiac ischemia-reperfusion in mice lacking UCP3 |
| title_full_unstemmed |
Energy substrate metabolism, mitochondrial structure and oxidative stress after cardiac ischemia-reperfusion in mice lacking UCP3 |
| title_sort |
Energy substrate metabolism, mitochondrial structure and oxidative stress after cardiac ischemia-reperfusion in mice lacking UCP3 |
| dc.creator.none.fl_str_mv |
Sánchez-Pérez, Patricia Mata, Ana M. Torp, May-Kristin López-Bernardo, Elia Heiestad, Christina M Aronsen, Jan Magnus Molina-Iracheta, Antonio Jiménez-Borreguero, Luis J García-Roves, Pablo Costa, Ana S H Frezza, Christian Murphy, Michael P Stenslokken, Kåre-Olav Cadenas, Susana |
| author |
Sánchez-Pérez, Patricia |
| author_facet |
Sánchez-Pérez, Patricia Mata, Ana M. Torp, May-Kristin López-Bernardo, Elia Heiestad, Christina M Aronsen, Jan Magnus Molina-Iracheta, Antonio Jiménez-Borreguero, Luis J García-Roves, Pablo Costa, Ana S H Frezza, Christian Murphy, Michael P Stenslokken, Kåre-Olav Cadenas, Susana |
| author_role |
author |
| author2 |
Mata, Ana M. Torp, May-Kristin López-Bernardo, Elia Heiestad, Christina M Aronsen, Jan Magnus Molina-Iracheta, Antonio Jiménez-Borreguero, Luis J García-Roves, Pablo Costa, Ana S H Frezza, Christian Murphy, Michael P Stenslokken, Kåre-Olav Cadenas, Susana |
| author2_role |
author author author author author author author author author author author author author |
| dc.contributor.none.fl_str_mv |
Instituto de Salud Carlos III Fundación Ramón Areces Banco Santander Consejo Superior de Investigaciones Científicas [https://ror.org/02gfc7t72] |
| dc.subject.none.fl_str_mv |
Energy metabolism Ischemia-reperfusion injury Mitochondrial respiration Mitochondrial structure Oxidative stress UCP3 (uncoupling protein 3) |
| topic |
Energy metabolism Ischemia-reperfusion injury Mitochondrial respiration Mitochondrial structure Oxidative stress UCP3 (uncoupling protein 3) |
| description |
Myocardial ischemia-reperfusion (IR) injury may result in cardiomyocyte dysfunction. Mitochondria play a critical role in cardiomyocyte recovery after IR injury. The mitochondrial uncoupling protein 3 (UCP3) has been proposed to reduce mitochondrial reactive oxygen species (ROS) production and to facilitate fatty acid oxidation. As both mechanisms might be protective following IR injury, we investigated functional, mitochondrial structural, and metabolic cardiac remodeling in wild-type mice and in mice lacking UCP3 (UCP3–KO) after IR. Results showed that infarct size in isolated perfused hearts subjected to IR ex vivo was larger in adult and old UCP3–KO mice than in equivalent wild-type mice, and was accompanied by higher levels of creatine kinase in the effluent and by more pronounced mitochondrial structural changes. The greater myocardial damage in UCP3–KO hearts was confirmed in vivo after coronary artery occlusion followed by reperfusion. S1QEL, a suppressor of superoxide generation from site I in complex I, limited infarct size in UCP3–KO hearts, pointing to exacerbated superoxide production as a possible cause of the damage. Metabolomics analysis of isolated perfused hearts confirmed the reported accumulation of succinate, xanthine and hypoxanthine during ischemia, and a shift to anaerobic glucose utilization, which all recovered upon reoxygenation. The metabolic response to ischemia and IR was similar in UCP3–KO and wild-type hearts, being lipid and energy metabolism the most affected pathways. Fatty acid oxidation and complex I (but not complex II) activity were equally impaired after IR. Overall, our results indicate that UCP3 deficiency promotes enhanced superoxide generation and mitochondrial structural changes that increase the vulnerability of the myocardium to IR injury. |
| publishDate |
2023 |
| dc.date.none.fl_str_mv |
2023 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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article |
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publishedVersion |
| dc.identifier.none.fl_str_mv |
http://hdl.handle.net/10261/347026 |
| url |
http://hdl.handle.net/10261/347026 |
| dc.language.none.fl_str_mv |
Inglés |
| language_invalid_str_mv |
Inglés |
| dc.relation.none.fl_str_mv |
http://dx.doi.org/10.1016/j.freeradbiomed.2023.05.014 Sí |
| dc.rights.none.fl_str_mv |
info:eu-repo/semantics/openAccess |
| eu_rights_str_mv |
openAccess |
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reponame:DIGITAL.CSIC. Repositorio Institucional del CSIC instname:Consejo Superior de Investigaciones Científicas (CSIC) |
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Consejo Superior de Investigaciones Científicas (CSIC) |
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DIGITAL.CSIC. Repositorio Institucional del CSIC |
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DIGITAL.CSIC. Repositorio Institucional del CSIC |
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1869419826958565376 |
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15,30478 |