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...

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Detalles Bibliográficos
Autores principales: Bell, James R., Vila Petroff, Martín Gerardo, Delbridge, Lea M. D.
Formato: Articulo
Lenguaje:Inglés
Publicado: 2014
Materias:
Ciencias Médicas
CaMKII
Cardiomyocyte death
Contractile function
Ischemia
Reperfusion
Acceso en línea:http://sedici.unlp.edu.ar/handle/10915/85554
Aporte de:
SEDICI (UNLP) de Universidad Nacional de La Plata
id I19-R120-10915-85554
record_format dspace
institution Universidad Nacional de La Plata
institution_str I-19
repository_str R-120
collection SEDICI (UNLP)
language Inglés
topic Ciencias Médicas
CaMKII
Cardiomyocyte death
Contractile function
Ischemia
Reperfusion
spellingShingle Ciencias Médicas
CaMKII
Cardiomyocyte death
Contractile function
Ischemia
Reperfusion
Bell, James R.
Vila Petroff, Martín Gerardo
Delbridge, Lea M. D.
CaMKII-dependent responses to ischemia and reperfusion challenges in the heart
topic_facet 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.
format Articulo
Articulo
author Bell, James R.
Vila Petroff, Martín Gerardo
Delbridge, Lea M. D.
author_facet Bell, James R.
Vila Petroff, Martín Gerardo
Delbridge, Lea M. D.
author_sort Bell, James R.
title CaMKII-dependent responses to ischemia and reperfusion challenges in the heart
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
publishDate 2014
url http://sedici.unlp.edu.ar/handle/10915/85554
work_keys_str_mv AT belljamesr camkiidependentresponsestoischemiaandreperfusionchallengesintheheart
AT vilapetroffmartingerardo camkiidependentresponsestoischemiaandreperfusionchallengesintheheart
AT delbridgeleamd camkiidependentresponsestoischemiaandreperfusionchallengesintheheart
bdutipo_str Repositorios
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