CaMKII-dependent responses to ischemia and reperfusion challenges in the heart

Ischemic heart disease is a leading cause of death, and there is considerable imperative to identify effective therapeutic interventions. Cardiomyocyte Ca2+ overload is a major cause of ischemia and reperfusion injury, initiating a cascade of events culminating in cardiomyocyte death, myocardial dys...

Descripción completa

Detalles Bibliográficos
Autores: Bell, James R., Vila Petroff, Martín Gerardo, Delbridge, Lea M. D.
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2014
País:Argentina
Institución:Universidad Nacional de La Plata
Repositorio:SEDICI (UNLP)
Idioma:inglés
OAI Identifier:oai:sedici.unlp.edu.ar:10915/85554
Acceso en línea:http://sedici.unlp.edu.ar/handle/10915/85554
Access Level:acceso abierto
Palabra clave:Ciencias Médicas
CaMKII
Cardiomyocyte death
Contractile function
Ischemia
Reperfusion
id AR_ad8fcba64cf94ba488b0a69d24beffd2
oai_identifier_str oai:sedici.unlp.edu.ar:10915/85554
network_acronym_str AR
network_name_str Argentina
repository_id_str
spelling CaMKII-dependent responses to ischemia and reperfusion challenges in the heartBell, James R.Vila Petroff, Martín GerardoDelbridge, Lea M. D.Ciencias MédicasCaMKIICardiomyocyte deathContractile functionIschemiaReperfusionIschemic heart disease is a leading cause of death, and there is considerable imperative to identify effective therapeutic interventions. Cardiomyocyte Ca2+ overload is a major cause of ischemia and reperfusion injury, initiating a cascade of events culminating in cardiomyocyte death, myocardial dysfunction, and occurrence of lethal arrhythmias. Responsive to fluctuations in intracellular Ca2+, Ca2+/calmodulin-dependent protein kinase II (CaMKII) has emerged as an enticing therapeutic target in the management of ischemic heart injury. CaMKII is activated early in ischemia and to a greater extent in the first few minutes of reperfusion, at a time when reperfusion arrhythmias are particularly prominent. CaMKII phosphorylates and upregulates many of the key proteins involved in intracellular Na+ and Ca2+ loading in ischemia and reperfusion. Experimentally, selective inhibition of CaMKII activity reduces cardiomyocyte death and arrhythmic incidence post-ischemia. New evidence is emerging that CaMKII actions in ischemia and reperfusion involve specific splice variant targeted actions, selective and localized post-translational modifications, and organelle-directed substrate interactions. A more complete mechanistic understanding of CaMKII mode of action in ischemia and reperfusion is required to optimize intervention opportunities. This review summarizes the current experimentally derived understanding of CaMKII participation in mediating the pathophysiology of the heart in ischemia and in reperfusion, and highlights priority future research directions.Centro de Investigaciones Cardiovasculares2014info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionArticulohttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfhttp://sedici.unlp.edu.ar/handle/10915/85554enginfo:eu-repo/semantics/altIdentifier/issn/1663-9812info:eu-repo/semantics/altIdentifier/doi/10.3389/fphar.2014.00096info:eu-repo/semantics/openAccesshttp://creativecommons.org/licenses/by-nc-sa/4.0/Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International (CC BY-NC-SA 4.0)reponame:SEDICI (UNLP)instname:Universidad Nacional de La Platainstacron:UNLP2024-05-08T12:54:24Zoai:sedici.unlp.edu.ar:10915/85554Institucionalhttp://sedici.unlp.edu.ar/Universidad públicaNo correspondehttp://sedici.unlp.edu.ar/oai/snrdalira@sedici.unlp.edu.arArgentinaNo correspondeNo correspondeNo correspondeopendoar:13292024-05-08 12:54:25.096SEDICI (UNLP) - Universidad Nacional de La Platafalse
dc.title.none.fl_str_mv CaMKII-dependent responses to ischemia and reperfusion challenges in the heart
title CaMKII-dependent responses to ischemia and reperfusion challenges in the heart
spellingShingle CaMKII-dependent responses to ischemia and reperfusion challenges in the heart
Bell, James R.
Ciencias Médicas
CaMKII
Cardiomyocyte death
Contractile function
Ischemia
Reperfusion
title_short CaMKII-dependent responses to ischemia and reperfusion challenges in the heart
title_full CaMKII-dependent responses to ischemia and reperfusion challenges in the heart
title_fullStr CaMKII-dependent responses to ischemia and reperfusion challenges in the heart
title_full_unstemmed CaMKII-dependent responses to ischemia and reperfusion challenges in the heart
title_sort CaMKII-dependent responses to ischemia and reperfusion challenges in the heart
dc.creator.none.fl_str_mv Bell, James R.
Vila Petroff, Martín Gerardo
Delbridge, Lea M. D.
author Bell, James R.
author_facet Bell, James R.
Vila Petroff, Martín Gerardo
Delbridge, Lea M. D.
author_role author
author2 Vila Petroff, Martín Gerardo
Delbridge, Lea M. D.
author2_role author
author
dc.subject.none.fl_str_mv Ciencias Médicas
CaMKII
Cardiomyocyte death
Contractile function
Ischemia
Reperfusion
topic Ciencias Médicas
CaMKII
Cardiomyocyte death
Contractile function
Ischemia
Reperfusion
description Ischemic heart disease is a leading cause of death, and there is considerable imperative to identify effective therapeutic interventions. Cardiomyocyte Ca2+ overload is a major cause of ischemia and reperfusion injury, initiating a cascade of events culminating in cardiomyocyte death, myocardial dysfunction, and occurrence of lethal arrhythmias. Responsive to fluctuations in intracellular Ca2+, Ca2+/calmodulin-dependent protein kinase II (CaMKII) has emerged as an enticing therapeutic target in the management of ischemic heart injury. CaMKII is activated early in ischemia and to a greater extent in the first few minutes of reperfusion, at a time when reperfusion arrhythmias are particularly prominent. CaMKII phosphorylates and upregulates many of the key proteins involved in intracellular Na+ and Ca2+ loading in ischemia and reperfusion. Experimentally, selective inhibition of CaMKII activity reduces cardiomyocyte death and arrhythmic incidence post-ischemia. New evidence is emerging that CaMKII actions in ischemia and reperfusion involve specific splice variant targeted actions, selective and localized post-translational modifications, and organelle-directed substrate interactions. A more complete mechanistic understanding of CaMKII mode of action in ischemia and reperfusion is required to optimize intervention opportunities. This review summarizes the current experimentally derived understanding of CaMKII participation in mediating the pathophysiology of the heart in ischemia and in reperfusion, and highlights priority future research directions.
publishDate 2014
dc.date.none.fl_str_mv 2014
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
Articulo
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://sedici.unlp.edu.ar/handle/10915/85554
url http://sedici.unlp.edu.ar/handle/10915/85554
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/issn/1663-9812
info:eu-repo/semantics/altIdentifier/doi/10.3389/fphar.2014.00096
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
http://creativecommons.org/licenses/by-nc-sa/4.0/
Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International (CC BY-NC-SA 4.0)
eu_rights_str_mv openAccess
rights_invalid_str_mv http://creativecommons.org/licenses/by-nc-sa/4.0/
Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International (CC BY-NC-SA 4.0)
dc.format.none.fl_str_mv application/pdf
dc.source.none.fl_str_mv reponame:SEDICI (UNLP)
instname:Universidad Nacional de La Plata
instacron:UNLP
instname_str Universidad Nacional de La Plata
instacron_str UNLP
institution UNLP
reponame_str SEDICI (UNLP)
collection SEDICI (UNLP)
repository.name.fl_str_mv SEDICI (UNLP) - Universidad Nacional de La Plata
repository.mail.fl_str_mv alira@sedici.unlp.edu.ar
_version_ 1799194214314016768
score 15,811543

Similares en LA Referencia