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
CONICET Digital (CONICET)
Institución
Consejo Nacional de Investigaciones Científicas y Técnicas
OAI Identificador
oai:ri.conicet.gov.ar:11336/96255
Acceder
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oai_identifier_str oai:ri.conicet.gov.ar:11336/96255
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling 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 Técnicas2025-10-22T11:01:41Zoai: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:34982025-10-22 11:01:41.876CONICET 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
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
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score 12.982451

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