Gαi2 - and Gαi3-deficient mice display opposite severity of myocardial ischemia reperfusion injury
- Autores
- Köhler, David; Devanathan, Vasudharani; De Franz, Claudia Bernardo Oliveira; Eldh, Therese; Novakovic, Ana; Roth, Judith M.; Granja, Tiago; Birnbaumer, Lutz; Rosenberger, Peter; Beer Hammer, Sandra; Nürnberg, Bernd
- Año de publicación
- 2014
- Idioma
- inglés
- Tipo de recurso
- artículo
- Estado
- versión publicada
- Descripción
- G-protein-coupled receptors (GPCRs) are the most abundant receptors in the heart and therefore are common targets for cardiovascular therapeutics. The activated GPCRs transduce their signals via heterotrimeric G-proteins. The four major families of G-proteins identified so far are specified through their α-subunit: Gαi, Gαs, Gαq and G12/13. Gαi-proteins have been reported to protect hearts from ischemia reperfusion injury. However, determining the individual impact of Gαi2 or Gαi3 on myocardial ischemia injury has not been clarified yet. Here, we first investigated expression of Gαi2 and Gαi3 on transcriptional level by quantitative PCR and on protein level by immunoblot analysis as well as by immunofluorescence in cardiac tissues of wild-type, Gαi2-, and Gαi3-deficient mice. Gαi2 was expressed at higher levels than Gαi3 in murine hearts, and irrespective of the isoform being knocked out we observed an up regulation of the remaining Gαi-protein. Myocardial ischemia promptly regulated cardiac mRNA and with a slight delay protein levels of both Gαi2 and Gαi3, indicating important roles for both Gαi isoforms. Furthermore, ischemia reperfusion injury in Gαi2- and Gαi3-deficient mice exhibited opposite outcomes. Whereas the absence of Gαi2 significantly increased the infarct size in the heart, the absence of Gαi3 or the concomitant upregulation of Gαi2 dramatically reduced cardiac infarction. In conclusion, we demonstrate for the first time that the genetic ablation of Gαi proteins has protective or deleterious effects on cardiac ischemia reperfusion injury depending on the isoform being absent.
Fil: Köhler, David. Eberhard Karls University Hospitals and Clinics; Alemania
Fil: Devanathan, Vasudharani. Eberhard Karls University Hospitals and Clinics; Alemania
Fil: De Franz, Claudia Bernardo Oliveira. Eberhard Karls University Hospitals and Clinics; Alemania
Fil: Eldh, Therese. Eberhard Karls University Hospitals and Clinics; Alemania
Fil: Novakovic, Ana. Eberhard Karls University Hospitals and Clinics; Alemania
Fil: Roth, Judith M.. Eberhard Karls University Hospitals and Clinics; Alemania
Fil: Granja, Tiago. Eberhard Karls University Hospitals and Clinics; Alemania
Fil: Birnbaumer, Lutz. National Institutes of Health; Estados Unidos. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Rosenberger, Peter. Eberhard Karls University Hospitals and Clinics; Alemania
Fil: Beer Hammer, Sandra. Eberhard Karls University Hospitals and Clinics; Alemania
Fil: Nürnberg, Bernd. Eberhard Karls University Hospitals and Clinics; Alemania - Materia
-
Gai2
Myocardial Ischemia - Nivel de accesibilidad
- acceso abierto
- Condiciones de uso
- https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
- Repositorio
- Institución
- Consejo Nacional de Investigaciones Científicas y Técnicas
- OAI Identificador
- oai:ri.conicet.gov.ar:11336/96255
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CONICET Digital (CONICET) |
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Gαi2 - and Gαi3-deficient mice display opposite severity of myocardial ischemia reperfusion injuryKöhler, DavidDevanathan, VasudharaniDe Franz, Claudia Bernardo OliveiraEldh, ThereseNovakovic, AnaRoth, Judith M.Granja, TiagoBirnbaumer, LutzRosenberger, PeterBeer Hammer, SandraNürnberg, BerndGai2Myocardial Ischemiahttps://purl.org/becyt/ford/1.6https://purl.org/becyt/ford/1G-protein-coupled receptors (GPCRs) are the most abundant receptors in the heart and therefore are common targets for cardiovascular therapeutics. The activated GPCRs transduce their signals via heterotrimeric G-proteins. The four major families of G-proteins identified so far are specified through their α-subunit: Gαi, Gαs, Gαq and G12/13. Gαi-proteins have been reported to protect hearts from ischemia reperfusion injury. However, determining the individual impact of Gαi2 or Gαi3 on myocardial ischemia injury has not been clarified yet. Here, we first investigated expression of Gαi2 and Gαi3 on transcriptional level by quantitative PCR and on protein level by immunoblot analysis as well as by immunofluorescence in cardiac tissues of wild-type, Gαi2-, and Gαi3-deficient mice. Gαi2 was expressed at higher levels than Gαi3 in murine hearts, and irrespective of the isoform being knocked out we observed an up regulation of the remaining Gαi-protein. Myocardial ischemia promptly regulated cardiac mRNA and with a slight delay protein levels of both Gαi2 and Gαi3, indicating important roles for both Gαi isoforms. Furthermore, ischemia reperfusion injury in Gαi2- and Gαi3-deficient mice exhibited opposite outcomes. Whereas the absence of Gαi2 significantly increased the infarct size in the heart, the absence of Gαi3 or the concomitant upregulation of Gαi2 dramatically reduced cardiac infarction. In conclusion, we demonstrate for the first time that the genetic ablation of Gαi proteins has protective or deleterious effects on cardiac ischemia reperfusion injury depending on the isoform being absent.Fil: Köhler, David. Eberhard Karls University Hospitals and Clinics; AlemaniaFil: Devanathan, Vasudharani. Eberhard Karls University Hospitals and Clinics; AlemaniaFil: De Franz, Claudia Bernardo Oliveira. Eberhard Karls University Hospitals and Clinics; AlemaniaFil: Eldh, Therese. Eberhard Karls University Hospitals and Clinics; AlemaniaFil: Novakovic, Ana. Eberhard Karls University Hospitals and Clinics; AlemaniaFil: Roth, Judith M.. Eberhard Karls University Hospitals and Clinics; AlemaniaFil: Granja, Tiago. Eberhard Karls University Hospitals and Clinics; AlemaniaFil: Birnbaumer, Lutz. National Institutes of Health; Estados Unidos. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Rosenberger, Peter. Eberhard Karls University Hospitals and Clinics; AlemaniaFil: Beer Hammer, Sandra. Eberhard Karls University Hospitals and Clinics; AlemaniaFil: Nürnberg, Bernd. Eberhard Karls University Hospitals and Clinics; AlemaniaPublic Library of Science2014-05info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/96255Köhler, David; Devanathan, Vasudharani; De Franz, Claudia Bernardo Oliveira; Eldh, Therese; Novakovic, Ana; et al.; Gαi2 - and Gαi3-deficient mice display opposite severity of myocardial ischemia reperfusion injury; Public Library of Science; Plos One; 9; 5; 5-2014; 1-81932-6203CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/url/https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0098325info:eu-repo/semantics/altIdentifier/doi/10.1371/journal.pone.0098325info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-29T09:33:39Zoai:ri.conicet.gov.ar:11336/96255instacron: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 09:33:40.05CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse |
dc.title.none.fl_str_mv |
Gαi2 - and Gαi3-deficient mice display opposite severity of myocardial ischemia reperfusion injury |
title |
Gαi2 - and Gαi3-deficient mice display opposite severity of myocardial ischemia reperfusion injury |
spellingShingle |
Gαi2 - and Gαi3-deficient mice display opposite severity of myocardial ischemia reperfusion injury Köhler, David Gai2 Myocardial Ischemia |
title_short |
Gαi2 - and Gαi3-deficient mice display opposite severity of myocardial ischemia reperfusion injury |
title_full |
Gαi2 - and Gαi3-deficient mice display opposite severity of myocardial ischemia reperfusion injury |
title_fullStr |
Gαi2 - and Gαi3-deficient mice display opposite severity of myocardial ischemia reperfusion injury |
title_full_unstemmed |
Gαi2 - and Gαi3-deficient mice display opposite severity of myocardial ischemia reperfusion injury |
title_sort |
Gαi2 - and Gαi3-deficient mice display opposite severity of myocardial ischemia reperfusion injury |
dc.creator.none.fl_str_mv |
Köhler, David Devanathan, Vasudharani De Franz, Claudia Bernardo Oliveira Eldh, Therese Novakovic, Ana Roth, Judith M. Granja, Tiago Birnbaumer, Lutz Rosenberger, Peter Beer Hammer, Sandra Nürnberg, Bernd |
author |
Köhler, David |
author_facet |
Köhler, David Devanathan, Vasudharani De Franz, Claudia Bernardo Oliveira Eldh, Therese Novakovic, Ana Roth, Judith M. Granja, Tiago Birnbaumer, Lutz Rosenberger, Peter Beer Hammer, Sandra Nürnberg, Bernd |
author_role |
author |
author2 |
Devanathan, Vasudharani De Franz, Claudia Bernardo Oliveira Eldh, Therese Novakovic, Ana Roth, Judith M. Granja, Tiago Birnbaumer, Lutz Rosenberger, Peter Beer Hammer, Sandra Nürnberg, Bernd |
author2_role |
author author author author author author author author author author |
dc.subject.none.fl_str_mv |
Gai2 Myocardial Ischemia |
topic |
Gai2 Myocardial Ischemia |
purl_subject.fl_str_mv |
https://purl.org/becyt/ford/1.6 https://purl.org/becyt/ford/1 |
dc.description.none.fl_txt_mv |
G-protein-coupled receptors (GPCRs) are the most abundant receptors in the heart and therefore are common targets for cardiovascular therapeutics. The activated GPCRs transduce their signals via heterotrimeric G-proteins. The four major families of G-proteins identified so far are specified through their α-subunit: Gαi, Gαs, Gαq and G12/13. Gαi-proteins have been reported to protect hearts from ischemia reperfusion injury. However, determining the individual impact of Gαi2 or Gαi3 on myocardial ischemia injury has not been clarified yet. Here, we first investigated expression of Gαi2 and Gαi3 on transcriptional level by quantitative PCR and on protein level by immunoblot analysis as well as by immunofluorescence in cardiac tissues of wild-type, Gαi2-, and Gαi3-deficient mice. Gαi2 was expressed at higher levels than Gαi3 in murine hearts, and irrespective of the isoform being knocked out we observed an up regulation of the remaining Gαi-protein. Myocardial ischemia promptly regulated cardiac mRNA and with a slight delay protein levels of both Gαi2 and Gαi3, indicating important roles for both Gαi isoforms. Furthermore, ischemia reperfusion injury in Gαi2- and Gαi3-deficient mice exhibited opposite outcomes. Whereas the absence of Gαi2 significantly increased the infarct size in the heart, the absence of Gαi3 or the concomitant upregulation of Gαi2 dramatically reduced cardiac infarction. In conclusion, we demonstrate for the first time that the genetic ablation of Gαi proteins has protective or deleterious effects on cardiac ischemia reperfusion injury depending on the isoform being absent. Fil: Köhler, David. Eberhard Karls University Hospitals and Clinics; Alemania Fil: Devanathan, Vasudharani. Eberhard Karls University Hospitals and Clinics; Alemania Fil: De Franz, Claudia Bernardo Oliveira. Eberhard Karls University Hospitals and Clinics; Alemania Fil: Eldh, Therese. Eberhard Karls University Hospitals and Clinics; Alemania Fil: Novakovic, Ana. Eberhard Karls University Hospitals and Clinics; Alemania Fil: Roth, Judith M.. Eberhard Karls University Hospitals and Clinics; Alemania Fil: Granja, Tiago. Eberhard Karls University Hospitals and Clinics; Alemania Fil: Birnbaumer, Lutz. National Institutes of Health; Estados Unidos. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina Fil: Rosenberger, Peter. Eberhard Karls University Hospitals and Clinics; Alemania Fil: Beer Hammer, Sandra. Eberhard Karls University Hospitals and Clinics; Alemania Fil: Nürnberg, Bernd. Eberhard Karls University Hospitals and Clinics; Alemania |
description |
G-protein-coupled receptors (GPCRs) are the most abundant receptors in the heart and therefore are common targets for cardiovascular therapeutics. The activated GPCRs transduce their signals via heterotrimeric G-proteins. The four major families of G-proteins identified so far are specified through their α-subunit: Gαi, Gαs, Gαq and G12/13. Gαi-proteins have been reported to protect hearts from ischemia reperfusion injury. However, determining the individual impact of Gαi2 or Gαi3 on myocardial ischemia injury has not been clarified yet. Here, we first investigated expression of Gαi2 and Gαi3 on transcriptional level by quantitative PCR and on protein level by immunoblot analysis as well as by immunofluorescence in cardiac tissues of wild-type, Gαi2-, and Gαi3-deficient mice. Gαi2 was expressed at higher levels than Gαi3 in murine hearts, and irrespective of the isoform being knocked out we observed an up regulation of the remaining Gαi-protein. Myocardial ischemia promptly regulated cardiac mRNA and with a slight delay protein levels of both Gαi2 and Gαi3, indicating important roles for both Gαi isoforms. Furthermore, ischemia reperfusion injury in Gαi2- and Gαi3-deficient mice exhibited opposite outcomes. Whereas the absence of Gαi2 significantly increased the infarct size in the heart, the absence of Gαi3 or the concomitant upregulation of Gαi2 dramatically reduced cardiac infarction. In conclusion, we demonstrate for the first time that the genetic ablation of Gαi proteins has protective or deleterious effects on cardiac ischemia reperfusion injury depending on the isoform being absent. |
publishDate |
2014 |
dc.date.none.fl_str_mv |
2014-05 |
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/11336/96255 Köhler, David; Devanathan, Vasudharani; De Franz, Claudia Bernardo Oliveira; Eldh, Therese; Novakovic, Ana; et al.; Gαi2 - and Gαi3-deficient mice display opposite severity of myocardial ischemia reperfusion injury; Public Library of Science; Plos One; 9; 5; 5-2014; 1-8 1932-6203 CONICET Digital CONICET |
url |
http://hdl.handle.net/11336/96255 |
identifier_str_mv |
Köhler, David; Devanathan, Vasudharani; De Franz, Claudia Bernardo Oliveira; Eldh, Therese; Novakovic, Ana; et al.; Gαi2 - and Gαi3-deficient mice display opposite severity of myocardial ischemia reperfusion injury; Public Library of Science; Plos One; 9; 5; 5-2014; 1-8 1932-6203 CONICET Digital CONICET |
dc.language.none.fl_str_mv |
eng |
language |
eng |
dc.relation.none.fl_str_mv |
info:eu-repo/semantics/altIdentifier/url/https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0098325 info:eu-repo/semantics/altIdentifier/doi/10.1371/journal.pone.0098325 |
dc.rights.none.fl_str_mv |
info:eu-repo/semantics/openAccess https://creativecommons.org/licenses/by-nc-sa/2.5/ar/ |
eu_rights_str_mv |
openAccess |
rights_invalid_str_mv |
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/ |
dc.format.none.fl_str_mv |
application/pdf application/pdf |
dc.publisher.none.fl_str_mv |
Public Library of Science |
publisher.none.fl_str_mv |
Public Library of Science |
dc.source.none.fl_str_mv |
reponame:CONICET Digital (CONICET) instname:Consejo Nacional de Investigaciones Científicas y Técnicas |
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CONICET Digital (CONICET) |
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CONICET Digital (CONICET) |
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Consejo Nacional de Investigaciones Científicas y Técnicas |
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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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1844613035998576640 |
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13.070432 |