High-Fat-Diet-Induced Obesity Produces Spontaneous Ventricular Arrhythmias and Increases the Activity of Ryanodine Receptors in Mice

Autores
Pecchi Sanchez, Gina Angela; Araneda, Felipe; Peña, Juan Pedro; Finkelstein, Jose Pablo; Riquelme, Jaime A.; Montecinos, Luis; Barrientos, Genaro; LLanos, Paola; Pedrozo, Zully; Said, Maria Matilde; Bull, Ricardo; Donoso, Paulina
Año de publicación
2018
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
Ventricular arrhythmias are a common cause of sudden cardiac death, and their occurrence is higher in obese subjects. Abnormal gating of ryanodine receptors (RyR2), the calcium release channels of the sarcoplasmic reticulum, can produce ventricular arrhythmias. Since obesity promotes oxidative stress and RyR2 are redox-sensitive channels, we investigated whether the RyR2 activity was altered in obese mice. Mice fed a high fat diet (HFD) became obese after eight weeks and exhibited a significant increase in the occurrence of ventricular arrhythmias. Single RyR2 channels isolated from the hearts of obese mice were more active in planar bilayers than those isolated from the hearts of the control mice. At the molecular level, RyR2 channels from HFD-fed mice had substantially fewer free thiol residues, suggesting that redox modifications were responsible for the higher activity. Apocynin, provided in the drinking water, completely prevented the appearance of ventricular arrhythmias in HFD-fed mice, and normalized the activity and content of the free thiol residues of the protein. HFD increased the expression of NOX4, an isoform of NADPH oxidase, in the heart. Our results suggest that HFD increases the activity of RyR2 channels via a redox-dependent mechanism, favoring the appearance of ventricular arrhythmias.
Fil: Pecchi Sanchez, Gina Angela. Universidad de Chile. Facultad de Medicina. Institutos de Ciencias Biomédicas; Chile
Fil: Araneda, Felipe. Universidad de Chile. Facultad de Medicina. Institutos de Ciencias Biomédicas; Chile
Fil: Peña, Juan Pedro. Universidad de Viña del Mar. Escuela de Ciencias Veterinarias; Chile
Fil: Finkelstein, Jose Pablo. Universidad de Chile. Facultad de Medicina. Institutos de Ciencias Biomédicas; Chile
Fil: Riquelme, Jaime A.. Universidad de Chile; Chile
Fil: Montecinos, Luis. Universidad de Chile. Facultad de Medicina. Institutos de Ciencias Biomédicas; Chile
Fil: Barrientos, Genaro. Universidad de Chile. Facultad de Medicina. Institutos de Ciencias Biomédicas; Chile
Fil: LLanos, Paola. Universidad de Chile; Chile
Fil: Pedrozo, Zully. Universidad de Chile. Facultad de Medicina. Institutos de Ciencias Biomédicas; Chile
Fil: Said, Maria Matilde. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Centro de Investigaciones Cardiovasculares "Dr. Horacio Eugenio Cingolani". Universidad Nacional de La Plata. Facultad de Ciencias Médicas. Centro de Investigaciones Cardiovasculares "Dr. Horacio Eugenio Cingolani"; Argentina
Fil: Bull, Ricardo. Universidad de Chile. Facultad de Medicina. Institutos de Ciencias Biomédicas; Chile
Fil: Donoso, Paulina. Universidad de Chile. Facultad de Medicina. Institutos de Ciencias Biomédicas; Chile
Materia
CALCIUM RELEASE CHANNELS
REACTIVE OXYGEN SPECIES
REDOX MODIFICATIONS
VENTRICULAR TACHYCARDIA
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:11336/113519
Acceder
id CONICETDig_22c92147d3a0d3b3e76f33b0d66e7f82
oai_identifier_str oai:ri.conicet.gov.ar:11336/113519
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling High-Fat-Diet-Induced Obesity Produces Spontaneous Ventricular Arrhythmias and Increases the Activity of Ryanodine Receptors in MicePecchi Sanchez, Gina AngelaAraneda, FelipePeña, Juan PedroFinkelstein, Jose PabloRiquelme, Jaime A.Montecinos, LuisBarrientos, GenaroLLanos, PaolaPedrozo, ZullySaid, Maria MatildeBull, RicardoDonoso, PaulinaCALCIUM RELEASE CHANNELSREACTIVE OXYGEN SPECIESREDOX MODIFICATIONSVENTRICULAR TACHYCARDIAhttps://purl.org/becyt/ford/3.1https://purl.org/becyt/ford/3Ventricular arrhythmias are a common cause of sudden cardiac death, and their occurrence is higher in obese subjects. Abnormal gating of ryanodine receptors (RyR2), the calcium release channels of the sarcoplasmic reticulum, can produce ventricular arrhythmias. Since obesity promotes oxidative stress and RyR2 are redox-sensitive channels, we investigated whether the RyR2 activity was altered in obese mice. Mice fed a high fat diet (HFD) became obese after eight weeks and exhibited a significant increase in the occurrence of ventricular arrhythmias. Single RyR2 channels isolated from the hearts of obese mice were more active in planar bilayers than those isolated from the hearts of the control mice. At the molecular level, RyR2 channels from HFD-fed mice had substantially fewer free thiol residues, suggesting that redox modifications were responsible for the higher activity. Apocynin, provided in the drinking water, completely prevented the appearance of ventricular arrhythmias in HFD-fed mice, and normalized the activity and content of the free thiol residues of the protein. HFD increased the expression of NOX4, an isoform of NADPH oxidase, in the heart. Our results suggest that HFD increases the activity of RyR2 channels via a redox-dependent mechanism, favoring the appearance of ventricular arrhythmias.Fil: Pecchi Sanchez, Gina Angela. Universidad de Chile. Facultad de Medicina. Institutos de Ciencias Biomédicas; ChileFil: Araneda, Felipe. Universidad de Chile. Facultad de Medicina. Institutos de Ciencias Biomédicas; ChileFil: Peña, Juan Pedro. Universidad de Viña del Mar. Escuela de Ciencias Veterinarias; ChileFil: Finkelstein, Jose Pablo. Universidad de Chile. Facultad de Medicina. Institutos de Ciencias Biomédicas; ChileFil: Riquelme, Jaime A.. Universidad de Chile; ChileFil: Montecinos, Luis. Universidad de Chile. Facultad de Medicina. Institutos de Ciencias Biomédicas; ChileFil: Barrientos, Genaro. Universidad de Chile. Facultad de Medicina. Institutos de Ciencias Biomédicas; ChileFil: LLanos, Paola. Universidad de Chile; ChileFil: Pedrozo, Zully. Universidad de Chile. Facultad de Medicina. Institutos de Ciencias Biomédicas; ChileFil: Said, Maria Matilde. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Centro de Investigaciones Cardiovasculares "Dr. Horacio Eugenio Cingolani". Universidad Nacional de La Plata. Facultad de Ciencias Médicas. Centro de Investigaciones Cardiovasculares "Dr. Horacio Eugenio Cingolani"; ArgentinaFil: Bull, Ricardo. Universidad de Chile. Facultad de Medicina. Institutos de Ciencias Biomédicas; ChileFil: Donoso, Paulina. Universidad de Chile. Facultad de Medicina. Institutos de Ciencias Biomédicas; ChileMolecular Diversity Preservation International2018-02-10info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/113519Pecchi Sanchez, Gina Angela; Araneda, Felipe; Peña, Juan Pedro; Finkelstein, Jose Pablo; Riquelme, Jaime A.; et al.; High-Fat-Diet-Induced Obesity Produces Spontaneous Ventricular Arrhythmias and Increases the Activity of Ryanodine Receptors in Mice; Molecular Diversity Preservation International; International Journal of Molecular Sciences; 19; 2; 10-2-2018; 1-151422-0067CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/url/https://www.mdpi.com/1422-0067/19/2/533info:eu-repo/semantics/altIdentifier/doi/10.3390/ijms19020533info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-10-22T12:04:56Zoai:ri.conicet.gov.ar:11336/113519instacron: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:34982025-10-22 12:04:56.681CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv High-Fat-Diet-Induced Obesity Produces Spontaneous Ventricular Arrhythmias and Increases the Activity of Ryanodine Receptors in Mice
title High-Fat-Diet-Induced Obesity Produces Spontaneous Ventricular Arrhythmias and Increases the Activity of Ryanodine Receptors in Mice
spellingShingle High-Fat-Diet-Induced Obesity Produces Spontaneous Ventricular Arrhythmias and Increases the Activity of Ryanodine Receptors in Mice
Pecchi Sanchez, Gina Angela
CALCIUM RELEASE CHANNELS
REACTIVE OXYGEN SPECIES
REDOX MODIFICATIONS
VENTRICULAR TACHYCARDIA
title_short High-Fat-Diet-Induced Obesity Produces Spontaneous Ventricular Arrhythmias and Increases the Activity of Ryanodine Receptors in Mice
title_full High-Fat-Diet-Induced Obesity Produces Spontaneous Ventricular Arrhythmias and Increases the Activity of Ryanodine Receptors in Mice
title_fullStr High-Fat-Diet-Induced Obesity Produces Spontaneous Ventricular Arrhythmias and Increases the Activity of Ryanodine Receptors in Mice
title_full_unstemmed High-Fat-Diet-Induced Obesity Produces Spontaneous Ventricular Arrhythmias and Increases the Activity of Ryanodine Receptors in Mice
title_sort High-Fat-Diet-Induced Obesity Produces Spontaneous Ventricular Arrhythmias and Increases the Activity of Ryanodine Receptors in Mice
dc.creator.none.fl_str_mv Pecchi Sanchez, Gina Angela
Araneda, Felipe
Peña, Juan Pedro
Finkelstein, Jose Pablo
Riquelme, Jaime A.
Montecinos, Luis
Barrientos, Genaro
LLanos, Paola
Pedrozo, Zully
Said, Maria Matilde
Bull, Ricardo
Donoso, Paulina
author Pecchi Sanchez, Gina Angela
author_facet Pecchi Sanchez, Gina Angela
Araneda, Felipe
Peña, Juan Pedro
Finkelstein, Jose Pablo
Riquelme, Jaime A.
Montecinos, Luis
Barrientos, Genaro
LLanos, Paola
Pedrozo, Zully
Said, Maria Matilde
Bull, Ricardo
Donoso, Paulina
author_role author
author2 Araneda, Felipe
Peña, Juan Pedro
Finkelstein, Jose Pablo
Riquelme, Jaime A.
Montecinos, Luis
Barrientos, Genaro
LLanos, Paola
Pedrozo, Zully
Said, Maria Matilde
Bull, Ricardo
Donoso, Paulina
author2_role author
author
author
author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv CALCIUM RELEASE CHANNELS
REACTIVE OXYGEN SPECIES
REDOX MODIFICATIONS
VENTRICULAR TACHYCARDIA
topic CALCIUM RELEASE CHANNELS
REACTIVE OXYGEN SPECIES
REDOX MODIFICATIONS
VENTRICULAR TACHYCARDIA
purl_subject.fl_str_mv https://purl.org/becyt/ford/3.1
https://purl.org/becyt/ford/3
dc.description.none.fl_txt_mv Ventricular arrhythmias are a common cause of sudden cardiac death, and their occurrence is higher in obese subjects. Abnormal gating of ryanodine receptors (RyR2), the calcium release channels of the sarcoplasmic reticulum, can produce ventricular arrhythmias. Since obesity promotes oxidative stress and RyR2 are redox-sensitive channels, we investigated whether the RyR2 activity was altered in obese mice. Mice fed a high fat diet (HFD) became obese after eight weeks and exhibited a significant increase in the occurrence of ventricular arrhythmias. Single RyR2 channels isolated from the hearts of obese mice were more active in planar bilayers than those isolated from the hearts of the control mice. At the molecular level, RyR2 channels from HFD-fed mice had substantially fewer free thiol residues, suggesting that redox modifications were responsible for the higher activity. Apocynin, provided in the drinking water, completely prevented the appearance of ventricular arrhythmias in HFD-fed mice, and normalized the activity and content of the free thiol residues of the protein. HFD increased the expression of NOX4, an isoform of NADPH oxidase, in the heart. Our results suggest that HFD increases the activity of RyR2 channels via a redox-dependent mechanism, favoring the appearance of ventricular arrhythmias.
Fil: Pecchi Sanchez, Gina Angela. Universidad de Chile. Facultad de Medicina. Institutos de Ciencias Biomédicas; Chile
Fil: Araneda, Felipe. Universidad de Chile. Facultad de Medicina. Institutos de Ciencias Biomédicas; Chile
Fil: Peña, Juan Pedro. Universidad de Viña del Mar. Escuela de Ciencias Veterinarias; Chile
Fil: Finkelstein, Jose Pablo. Universidad de Chile. Facultad de Medicina. Institutos de Ciencias Biomédicas; Chile
Fil: Riquelme, Jaime A.. Universidad de Chile; Chile
Fil: Montecinos, Luis. Universidad de Chile. Facultad de Medicina. Institutos de Ciencias Biomédicas; Chile
Fil: Barrientos, Genaro. Universidad de Chile. Facultad de Medicina. Institutos de Ciencias Biomédicas; Chile
Fil: LLanos, Paola. Universidad de Chile; Chile
Fil: Pedrozo, Zully. Universidad de Chile. Facultad de Medicina. Institutos de Ciencias Biomédicas; Chile
Fil: Said, Maria Matilde. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Centro de Investigaciones Cardiovasculares "Dr. Horacio Eugenio Cingolani". Universidad Nacional de La Plata. Facultad de Ciencias Médicas. Centro de Investigaciones Cardiovasculares "Dr. Horacio Eugenio Cingolani"; Argentina
Fil: Bull, Ricardo. Universidad de Chile. Facultad de Medicina. Institutos de Ciencias Biomédicas; Chile
Fil: Donoso, Paulina. Universidad de Chile. Facultad de Medicina. Institutos de Ciencias Biomédicas; Chile
description Ventricular arrhythmias are a common cause of sudden cardiac death, and their occurrence is higher in obese subjects. Abnormal gating of ryanodine receptors (RyR2), the calcium release channels of the sarcoplasmic reticulum, can produce ventricular arrhythmias. Since obesity promotes oxidative stress and RyR2 are redox-sensitive channels, we investigated whether the RyR2 activity was altered in obese mice. Mice fed a high fat diet (HFD) became obese after eight weeks and exhibited a significant increase in the occurrence of ventricular arrhythmias. Single RyR2 channels isolated from the hearts of obese mice were more active in planar bilayers than those isolated from the hearts of the control mice. At the molecular level, RyR2 channels from HFD-fed mice had substantially fewer free thiol residues, suggesting that redox modifications were responsible for the higher activity. Apocynin, provided in the drinking water, completely prevented the appearance of ventricular arrhythmias in HFD-fed mice, and normalized the activity and content of the free thiol residues of the protein. HFD increased the expression of NOX4, an isoform of NADPH oxidase, in the heart. Our results suggest that HFD increases the activity of RyR2 channels via a redox-dependent mechanism, favoring the appearance of ventricular arrhythmias.
publishDate 2018
dc.date.none.fl_str_mv 2018-02-10
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/11336/113519
Pecchi Sanchez, Gina Angela; Araneda, Felipe; Peña, Juan Pedro; Finkelstein, Jose Pablo; Riquelme, Jaime A.; et al.; High-Fat-Diet-Induced Obesity Produces Spontaneous Ventricular Arrhythmias and Increases the Activity of Ryanodine Receptors in Mice; Molecular Diversity Preservation International; International Journal of Molecular Sciences; 19; 2; 10-2-2018; 1-15
1422-0067
CONICET Digital
CONICET
url http://hdl.handle.net/11336/113519
identifier_str_mv Pecchi Sanchez, Gina Angela; Araneda, Felipe; Peña, Juan Pedro; Finkelstein, Jose Pablo; Riquelme, Jaime A.; et al.; High-Fat-Diet-Induced Obesity Produces Spontaneous Ventricular Arrhythmias and Increases the Activity of Ryanodine Receptors in Mice; Molecular Diversity Preservation International; International Journal of Molecular Sciences; 19; 2; 10-2-2018; 1-15
1422-0067
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/url/https://www.mdpi.com/1422-0067/19/2/533
info:eu-repo/semantics/altIdentifier/doi/10.3390/ijms19020533
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
dc.publisher.none.fl_str_mv Molecular Diversity Preservation International
publisher.none.fl_str_mv Molecular Diversity Preservation International
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
_version_ 1846782400631144448
score 12.982451

Publicaciones similares