Reversible redox modifications of ryanodine receptor ameliorate ventricular arrhythmias in the ischemic-reperfused heart

Previous results from our laboratory showed that phosphorylation of ryanodine receptor 2 (RyR2) by Ca21 calmodulin-dependent kinase II (CaMKII) was a critical but not the unique event responsible for the production of reperfusion-induced arrhythmogenesis, suggesting the existence of other mechanisms...

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Autores principales: Becerra, Romina Valeria, Román, Bárbara Soledad, Di Carlo, Mariano Nahuel, Mariángelo, Juan Ignacio Elio, Salas, Margarita Ana, Sánchez, Gina, Donoso, Paulina, Schinella, Guillermo Raúl, Vittone, Leticia, Wehrens, Xander H., Mundiña-Weilenmann, Cecilia, Said, María Matilde
Formato: Articulo
Lenguaje:Inglés
Publicado: 2016
Materias:
Ciencias Médicas
arrhythmias
ischemia/reperfusion
ryanodine receptor type 2
redox modifications
Acceso en línea:http://sedici.unlp.edu.ar/handle/10915/103856
Aporte de:
SEDICI (UNLP) de Universidad Nacional de La Plata
id I19-R120-10915-103856
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
arrhythmias
ischemia/reperfusion
ryanodine receptor type 2
redox modifications
spellingShingle Ciencias Médicas
arrhythmias
ischemia/reperfusion
ryanodine receptor type 2
redox modifications
Becerra, Romina Valeria
Román, Bárbara Soledad
Di Carlo, Mariano Nahuel
Mariángelo, Juan Ignacio Elio
Salas, Margarita Ana
Sánchez, Gina
Donoso, Paulina
Schinella, Guillermo Raúl
Vittone, Leticia
Wehrens, Xander H.
Mundiña-Weilenmann, Cecilia
Said, María Matilde
Reversible redox modifications of ryanodine receptor ameliorate ventricular arrhythmias in the ischemic-reperfused heart
topic_facet Ciencias Médicas
arrhythmias
ischemia/reperfusion
ryanodine receptor type 2
redox modifications
description Previous results from our laboratory showed that phosphorylation of ryanodine receptor 2 (RyR2) by Ca21 calmodulin-dependent kinase II (CaMKII) was a critical but not the unique event responsible for the production of reperfusion-induced arrhythmogenesis, suggesting the existence of other mechanisms cooperating in an additive way to produce these rhythm alterations. Oxidative stress is a prominent feature of ischemia/reperfusion injury. Both CaMKII and RyR2 are proteins susceptible to alteration by redox modifications. This study was designed to elucidate whether CaMKII and RyR2 redox changes occur during reperfusion and whether these changes are involved in the genesis of arrhythmias. Langendorff-perfused hearts from rats or transgenic mice with genetic ablation of CaMKII phosphorylation site on RyR2 (S2814A) were subjected to ischemia-reperfusion in the presence or absence of a free radical scavenger (mercaptopropionylglycine, MPG) or inhibitors of NADPH oxidase and nitric oxide synthase. Left ventricular contractile parameters and monophasic action potentials were recorded. Oxidation and phosphorylation of CaMKII and RyR2 were assessed. Increased oxidation of CaMKII during reperfusion had no consequences on the level of RyR2 phosphorylation. Avoiding the reperfusion-induced thiol oxidation of RyR2 with MPG produced a reduction in the number of arrhythmias and did not modify the contractile recovery. Conversely, selective prevention of S-nitrosylation and S-glutathionylation of RyR2 was associated with higher numbers of arrhythmias and impaired contractility. In S2814A mice, treatment with MPG further reduced the incidence of arrhythmias. Taken together, the results suggest that redox modification of RyR2 synergistically with CaMKII phosphorylation modulates reperfusion arrhythmias.
format Articulo
Articulo
author Becerra, Romina Valeria
Román, Bárbara Soledad
Di Carlo, Mariano Nahuel
Mariángelo, Juan Ignacio Elio
Salas, Margarita Ana
Sánchez, Gina
Donoso, Paulina
Schinella, Guillermo Raúl
Vittone, Leticia
Wehrens, Xander H.
Mundiña-Weilenmann, Cecilia
Said, María Matilde
author_facet Becerra, Romina Valeria
Román, Bárbara Soledad
Di Carlo, Mariano Nahuel
Mariángelo, Juan Ignacio Elio
Salas, Margarita Ana
Sánchez, Gina
Donoso, Paulina
Schinella, Guillermo Raúl
Vittone, Leticia
Wehrens, Xander H.
Mundiña-Weilenmann, Cecilia
Said, María Matilde
author_sort Becerra, Romina Valeria
title Reversible redox modifications of ryanodine receptor ameliorate ventricular arrhythmias in the ischemic-reperfused heart
title_short Reversible redox modifications of ryanodine receptor ameliorate ventricular arrhythmias in the ischemic-reperfused heart
title_full Reversible redox modifications of ryanodine receptor ameliorate ventricular arrhythmias in the ischemic-reperfused heart
title_fullStr Reversible redox modifications of ryanodine receptor ameliorate ventricular arrhythmias in the ischemic-reperfused heart
title_full_unstemmed Reversible redox modifications of ryanodine receptor ameliorate ventricular arrhythmias in the ischemic-reperfused heart
title_sort reversible redox modifications of ryanodine receptor ameliorate ventricular arrhythmias in the ischemic-reperfused heart
publishDate 2016
url http://sedici.unlp.edu.ar/handle/10915/103856
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