Aging and CaMKII alter intracellular Ca2+ transients and heart rhythm in Drosophila Melanogaster

Autores
Santalla, Manuela; Valverde, Carlos Alfredo; Harnichar, Alejandro Ezequiel; Lacunza, Ezequiel; Aguilar Fuentes, Javier; Mattiazzi, Ramona Alicia; Ferrero, Paola Viviana
Año de publicación
2014
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
Aging is associated to disrupted contractility and rhythmicity, among other cardiovascular alterations. Drosophila melanogaster shows a pattern of aging similar to human beings and recapitulates the arrhythmogenic conditions found in the human heart. Moreover, the kinase CaMKII has been characterized as an important regulator of heart function and an arrhythmogenic molecule that participate in Ca2+ handling. Using a genetically engineered expressed Ca2+ indicator, we report changes in cardiac Ca2+ handling at two different ages. Aging prolonged relaxation, reduced spontaneous heart rate (HR) and increased the occurrence of arrhythmias, ectopic beats and asystoles. Alignment between Drosophila melanogaster and human CaMKII showed a high degree of conservation and indicates that relevant phosphorylation sites in humans are also present in the fruit fly. Inhibition of CaMKII by KN-93 (CaMKII-specific inhibitor), reduced HR without significant changes in other parameters. By contrast, overexpression of CaMKII increased HR and reduced arrhythmias. Moreover, it increased fluorescence amplitude, maximal rate of rise of fluorescence and reduced time to peak fluorescence. These results suggest that CaMKII in Drosophila melanogaster acts directly on heart function and that increasing CaMKII expression levels could be beneficial to improve contractility.
Fil: Santalla, Manuela. 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. Universidad Nacional del Noroeste de la Provincia de Buenos Aires. Departamento de Ciencias Básicas y Experimentales; Argentina
Fil: Valverde, Carlos Alfredo. 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
Fil: Harnichar, Alejandro Ezequiel. 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
Fil: Lacunza, Ezequiel. Universidad Nacional de La Plata. Facultad de Ciencias Medicas. Centro de Investigaciones Inmunologicas Basicas y Aplicadas; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Aguilar Fuentes, Javier. Universidad Autónoma de Chiapas; México
Fil: Mattiazzi, Ramona Alicia. 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
Fil: Ferrero, Paola Viviana. 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. Universidad Nacional del Noroeste de la Provincia de Buenos Aires. Departamento de Ciencias Básicas y Experimentales; Argentina
Materia
HEART
DROSOPHILA MELANOGASTER
AGING
CAMKII
TRANSCIENT CA2+
Nivel de accesibilidad
acceso abierto
Condiciones de uso
https://creativecommons.org/licenses/by/2.5/ar/
Repositorio
CONICET Digital (CONICET)
Institución
Consejo Nacional de Investigaciones Científicas y Técnicas
OAI Identificador
oai:ri.conicet.gov.ar:11336/12278
Acceder
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network_name_str CONICET Digital (CONICET)
spelling Aging and CaMKII alter intracellular Ca2+ transients and heart rhythm in Drosophila MelanogasterSantalla, ManuelaValverde, Carlos AlfredoHarnichar, Alejandro EzequielLacunza, EzequielAguilar Fuentes, JavierMattiazzi, Ramona AliciaFerrero, Paola VivianaHEARTDROSOPHILA MELANOGASTERAGINGCAMKIITRANSCIENT CA2+https://purl.org/becyt/ford/1.6https://purl.org/becyt/ford/1Aging is associated to disrupted contractility and rhythmicity, among other cardiovascular alterations. Drosophila melanogaster shows a pattern of aging similar to human beings and recapitulates the arrhythmogenic conditions found in the human heart. Moreover, the kinase CaMKII has been characterized as an important regulator of heart function and an arrhythmogenic molecule that participate in Ca2+ handling. Using a genetically engineered expressed Ca2+ indicator, we report changes in cardiac Ca2+ handling at two different ages. Aging prolonged relaxation, reduced spontaneous heart rate (HR) and increased the occurrence of arrhythmias, ectopic beats and asystoles. Alignment between Drosophila melanogaster and human CaMKII showed a high degree of conservation and indicates that relevant phosphorylation sites in humans are also present in the fruit fly. Inhibition of CaMKII by KN-93 (CaMKII-specific inhibitor), reduced HR without significant changes in other parameters. By contrast, overexpression of CaMKII increased HR and reduced arrhythmias. Moreover, it increased fluorescence amplitude, maximal rate of rise of fluorescence and reduced time to peak fluorescence. These results suggest that CaMKII in Drosophila melanogaster acts directly on heart function and that increasing CaMKII expression levels could be beneficial to improve contractility.Fil: Santalla, Manuela. 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. Universidad Nacional del Noroeste de la Provincia de Buenos Aires. Departamento de Ciencias Básicas y Experimentales; ArgentinaFil: Valverde, Carlos Alfredo. 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; ArgentinaFil: Harnichar, Alejandro Ezequiel. 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; ArgentinaFil: Lacunza, Ezequiel. Universidad Nacional de La Plata. Facultad de Ciencias Medicas. Centro de Investigaciones Inmunologicas Basicas y Aplicadas; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Aguilar Fuentes, Javier. Universidad Autónoma de Chiapas; MéxicoFil: Mattiazzi, Ramona Alicia. 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; ArgentinaFil: Ferrero, Paola Viviana. 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. Universidad Nacional del Noroeste de la Provincia de Buenos Aires. Departamento de Ciencias Básicas y Experimentales; ArgentinaPublic Library Of Science2014-07info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfapplication/pdfapplication/pdfapplication/pdfapplication/pdfapplication/pdfapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/12278Santalla, Manuela; Valverde, Carlos Alfredo; Harnichar, Alejandro Ezequiel; Lacunza, Ezequiel; Aguilar Fuentes, Javier; et al.; Aging and CaMKII alter intracellular Ca2+ transients and heart rhythm in Drosophila Melanogaster; Public Library Of Science; Plos One; 9; 7; 7-2014; 1-10; e1018711932-6203enginfo:eu-repo/semantics/altIdentifier/doi/10.1371/journal.pone.0101871info:eu-repo/semantics/altIdentifier/url/http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0101871info:eu-repo/semantics/altIdentifier/url/https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4087024/info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-17T11:53:11Zoai:ri.conicet.gov.ar:11336/12278instacron: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:34982025-09-17 11:53:11.686CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Aging and CaMKII alter intracellular Ca2+ transients and heart rhythm in Drosophila Melanogaster
title Aging and CaMKII alter intracellular Ca2+ transients and heart rhythm in Drosophila Melanogaster
spellingShingle Aging and CaMKII alter intracellular Ca2+ transients and heart rhythm in Drosophila Melanogaster
Santalla, Manuela
HEART
DROSOPHILA MELANOGASTER
AGING
CAMKII
TRANSCIENT CA2+
title_short Aging and CaMKII alter intracellular Ca2+ transients and heart rhythm in Drosophila Melanogaster
title_full Aging and CaMKII alter intracellular Ca2+ transients and heart rhythm in Drosophila Melanogaster
title_fullStr Aging and CaMKII alter intracellular Ca2+ transients and heart rhythm in Drosophila Melanogaster
title_full_unstemmed Aging and CaMKII alter intracellular Ca2+ transients and heart rhythm in Drosophila Melanogaster
title_sort Aging and CaMKII alter intracellular Ca2+ transients and heart rhythm in Drosophila Melanogaster
dc.creator.none.fl_str_mv Santalla, Manuela
Valverde, Carlos Alfredo
Harnichar, Alejandro Ezequiel
Lacunza, Ezequiel
Aguilar Fuentes, Javier
Mattiazzi, Ramona Alicia
Ferrero, Paola Viviana
author Santalla, Manuela
author_facet Santalla, Manuela
Valverde, Carlos Alfredo
Harnichar, Alejandro Ezequiel
Lacunza, Ezequiel
Aguilar Fuentes, Javier
Mattiazzi, Ramona Alicia
Ferrero, Paola Viviana
author_role author
author2 Valverde, Carlos Alfredo
Harnichar, Alejandro Ezequiel
Lacunza, Ezequiel
Aguilar Fuentes, Javier
Mattiazzi, Ramona Alicia
Ferrero, Paola Viviana
author2_role author
author
author
author
author
author
dc.subject.none.fl_str_mv HEART
DROSOPHILA MELANOGASTER
AGING
CAMKII
TRANSCIENT CA2+
topic HEART
DROSOPHILA MELANOGASTER
AGING
CAMKII
TRANSCIENT CA2+
purl_subject.fl_str_mv https://purl.org/becyt/ford/1.6
https://purl.org/becyt/ford/1
dc.description.none.fl_txt_mv Aging is associated to disrupted contractility and rhythmicity, among other cardiovascular alterations. Drosophila melanogaster shows a pattern of aging similar to human beings and recapitulates the arrhythmogenic conditions found in the human heart. Moreover, the kinase CaMKII has been characterized as an important regulator of heart function and an arrhythmogenic molecule that participate in Ca2+ handling. Using a genetically engineered expressed Ca2+ indicator, we report changes in cardiac Ca2+ handling at two different ages. Aging prolonged relaxation, reduced spontaneous heart rate (HR) and increased the occurrence of arrhythmias, ectopic beats and asystoles. Alignment between Drosophila melanogaster and human CaMKII showed a high degree of conservation and indicates that relevant phosphorylation sites in humans are also present in the fruit fly. Inhibition of CaMKII by KN-93 (CaMKII-specific inhibitor), reduced HR without significant changes in other parameters. By contrast, overexpression of CaMKII increased HR and reduced arrhythmias. Moreover, it increased fluorescence amplitude, maximal rate of rise of fluorescence and reduced time to peak fluorescence. These results suggest that CaMKII in Drosophila melanogaster acts directly on heart function and that increasing CaMKII expression levels could be beneficial to improve contractility.
Fil: Santalla, Manuela. 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. Universidad Nacional del Noroeste de la Provincia de Buenos Aires. Departamento de Ciencias Básicas y Experimentales; Argentina
Fil: Valverde, Carlos Alfredo. 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
Fil: Harnichar, Alejandro Ezequiel. 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
Fil: Lacunza, Ezequiel. Universidad Nacional de La Plata. Facultad de Ciencias Medicas. Centro de Investigaciones Inmunologicas Basicas y Aplicadas; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Aguilar Fuentes, Javier. Universidad Autónoma de Chiapas; México
Fil: Mattiazzi, Ramona Alicia. 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
Fil: Ferrero, Paola Viviana. 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. Universidad Nacional del Noroeste de la Provincia de Buenos Aires. Departamento de Ciencias Básicas y Experimentales; Argentina
description Aging is associated to disrupted contractility and rhythmicity, among other cardiovascular alterations. Drosophila melanogaster shows a pattern of aging similar to human beings and recapitulates the arrhythmogenic conditions found in the human heart. Moreover, the kinase CaMKII has been characterized as an important regulator of heart function and an arrhythmogenic molecule that participate in Ca2+ handling. Using a genetically engineered expressed Ca2+ indicator, we report changes in cardiac Ca2+ handling at two different ages. Aging prolonged relaxation, reduced spontaneous heart rate (HR) and increased the occurrence of arrhythmias, ectopic beats and asystoles. Alignment between Drosophila melanogaster and human CaMKII showed a high degree of conservation and indicates that relevant phosphorylation sites in humans are also present in the fruit fly. Inhibition of CaMKII by KN-93 (CaMKII-specific inhibitor), reduced HR without significant changes in other parameters. By contrast, overexpression of CaMKII increased HR and reduced arrhythmias. Moreover, it increased fluorescence amplitude, maximal rate of rise of fluorescence and reduced time to peak fluorescence. These results suggest that CaMKII in Drosophila melanogaster acts directly on heart function and that increasing CaMKII expression levels could be beneficial to improve contractility.
publishDate 2014
dc.date.none.fl_str_mv 2014-07
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/11336/12278
Santalla, Manuela; Valverde, Carlos Alfredo; Harnichar, Alejandro Ezequiel; Lacunza, Ezequiel; Aguilar Fuentes, Javier; et al.; Aging and CaMKII alter intracellular Ca2+ transients and heart rhythm in Drosophila Melanogaster; Public Library Of Science; Plos One; 9; 7; 7-2014; 1-10; e101871
1932-6203
url http://hdl.handle.net/11336/12278
identifier_str_mv Santalla, Manuela; Valverde, Carlos Alfredo; Harnichar, Alejandro Ezequiel; Lacunza, Ezequiel; Aguilar Fuentes, Javier; et al.; Aging and CaMKII alter intracellular Ca2+ transients and heart rhythm in Drosophila Melanogaster; Public Library Of Science; Plos One; 9; 7; 7-2014; 1-10; e101871
1932-6203
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/doi/10.1371/journal.pone.0101871
info:eu-repo/semantics/altIdentifier/url/http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0101871
info:eu-repo/semantics/altIdentifier/url/https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4087024/
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
https://creativecommons.org/licenses/by/2.5/ar/
eu_rights_str_mv openAccess
rights_invalid_str_mv https://creativecommons.org/licenses/by/2.5/ar/
dc.format.none.fl_str_mv application/pdf
application/pdf
application/pdf
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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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