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dc.contributor.author
Donoso, Paulin
dc.contributor.author
Finkelstein, José Pablo
dc.contributor.author
Montecinos, Luis
dc.contributor.author
Said, Matilde
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Sánchez, Gina
dc.contributor.author
Vittone, Leticia Beatriz
dc.contributor.author
Bull, Ricardo
dc.date.available
2017-01-25T20:34:05Z
dc.date.issued
2014-03
dc.identifier.citation
Donoso, Paulin; Finkelstein, José Pablo; Montecinos, Luis; Said, Matilde; Sánchez, Gina; et al.; Stimulation of NOX2 in isolated hearts reversibly sensitizes RyR2 channels to activation by cytoplasmic calcium; Elsevier; Journal Of Molecular And Cellular Cardiology; 68; 3-2014; 38–46
dc.identifier.issn
0022-2828
dc.identifier.uri
http://hdl.handle.net/11336/11952
dc.description.abstract
The response of ryanodine receptor (RyR) channels to cytoplasmic free calcium concentration ([Ca2 +]) is redox sensitive. Here, we report the effects of a mild oxidative stress on cardiac RyR (RyR2) channels in Langendorff perfused rat hearts. Single RyR2 channels from control ventricles displayed the same three responses to Ca2 + reported in other mammalian tissues, characterized by low, moderate, or high maximal activation. A single episode of 5 min of global ischemia, followed by 1 min of reperfusion, enhanced 2.3-fold the activity of NOX2 compared to controls and changed the frequency distribution of the different responses of RyR2 channels to calcium, favoring the more active ones: high activity response increased and low activity response decreased with respect to controls. This change was fully prevented by perfusion with apocynin or VAS 2870 before ischemia and totally reversed by the extension of the reperfusion period to 15 min. In vitro activation of NOX2 in control SR vesicles mimicked the effect of the ischemia/reperfusion episode on the frequencies of emergence of single RyR2 channel responses to [Ca2 +] and increased 2.2-fold the rate of calcium release in Ca2 +-loaded SR vesicles. In vitro changes were reversed at the single channel level by DTT and in isolated SR vesicles by glutaredoxin. Our results indicate that in whole hearts a mild oxidative stress enhances the response of cardiac RyR2 channels to calcium via NOX2 activation, probably by S-glutathionylation of RyR2 protein. This change is transitory and fully reversible, suggesting a possible role of redox modification in the physiological response of cardiac RyR2 to cellular calcium influx.
dc.format
application/pdf
dc.language.iso
eng
dc.publisher
Elsevier
dc.rights
info:eu-repo/semantics/openAccess
dc.rights.uri
https://creativecommons.org/licenses/by-nc-nd/2.5/ar/
dc.subject
Ca2 +-Induced Ca2 + Release
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Redox Signaling
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Single Channel
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Preconditioning
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Ischemia/Reperfusion
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Fisiología
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Medicina Básica
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CIENCIAS MÉDICAS Y DE LA SALUD
dc.title
Stimulation of NOX2 in isolated hearts reversibly sensitizes RyR2 channels to activation by cytoplasmic calcium
dc.type
info:eu-repo/semantics/article
dc.type
info:ar-repo/semantics/artículo
dc.type
info:eu-repo/semantics/publishedVersion
dc.date.updated
2017-01-25T13:58:11Z
dc.journal.volume
68
dc.journal.pagination
38–46
dc.journal.pais
Países Bajos
dc.journal.ciudad
Amsterdam
dc.description.fil
Fil: Donoso, Paulin. Universidad de Chile; Chile
dc.description.fil
Fil: Finkelstein, José Pablo. Universidad de Chile; Chile
dc.description.fil
Fil: Montecinos, Luis. Universidad de Chile; Chile
dc.description.fil
Fil: Said, Matilde. Consejo Nacional de Investigaciones Cientificas y Tecnicas. Centro Cientifico Tecnológico la Plata. Centro de Investigaciones Cardiovasculares "dr. Horacio Eugenio Cingolani"; Argentina. Universidad Nacional de la Plata. Facultad de Ciencias Médicas; Argentina
dc.description.fil
Fil: Sánchez, Gina. Universidad de Chile; Chile
dc.description.fil
Fil: Vittone, Leticia Beatriz. Consejo Nacional de Investigaciones Cientificas y Tecnicas. Centro Cientifico Tecnológico la Plata. Centro de Investigaciones Cardiovasculares "dr. Horacio Eugenio Cingolani"; Argentina. Universidad Nacional de la Plata. Facultad de Ciencias Médicas; Argentina
dc.description.fil
Fil: Bull, Ricardo. Universidad de Chile; Chile
dc.journal.title
Journal Of Molecular And Cellular Cardiology
dc.relation.alternativeid
info:eu-repo/semantics/altIdentifier/doi/http://dx.doi.org/10.1016/j.yjmcc.2013.12.028
dc.relation.alternativeid
info:eu-repo/semantics/altIdentifier/url/http://www.sciencedirect.com/science/article/pii/S0022282814000066
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