Ryanodine receptor phosphorylation by CaMKII promotes spontaneous Ca2+ release events in a rodent model of early stage diabetes: The arrhythmogenic substrate

Background: Heart failure and arrhythmias occur more frequently in patients with type 2 diabetes (T2DM) than in the general population. T2DM is preceded by a prediabetic condition marked by elevated reactive oxygen species (ROS) and subclinical cardiovascular defects. Although multifunctional Ca2+ c...

Descripción completa

Detalles Bibliográficos
Autores principales: Sommese, Leandro Matías, Valverde, Carlos Alfredo, Blanco, Paula Graciela, Castro, María Cecilia, Vélez Rueda, Jorge Omar, Kaetzel, Marcia, Dedman, John, Anderson, Mark E., Mattiazzi, Ramona Alicia, Palomeque, Julieta
Formato: Articulo Preprint
Lenguaje:Inglés
Publicado: 2016
Materias:
Ciencias Médicas
Arrhythmias
Prediabetes
Impaired glucose tolerance
Camkii
Ryanodine receptor
Acceso en línea:http://sedici.unlp.edu.ar/handle/10915/96349
https://ri.conicet.gov.ar/11336/12294
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4872299/
Aporte de:
SEDICI (UNLP) de Universidad Nacional de La Plata
id I19-R120-10915-96349
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
Prediabetes
Impaired glucose tolerance
Camkii
Ryanodine receptor
spellingShingle Ciencias Médicas
Arrhythmias
Prediabetes
Impaired glucose tolerance
Camkii
Ryanodine receptor
Sommese, Leandro Matías
Valverde, Carlos Alfredo
Blanco, Paula Graciela
Castro, María Cecilia
Vélez Rueda, Jorge Omar
Kaetzel, Marcia
Dedman, John
Anderson, Mark E.
Mattiazzi, Ramona Alicia
Palomeque, Julieta
Ryanodine receptor phosphorylation by CaMKII promotes spontaneous Ca2+ release events in a rodent model of early stage diabetes: The arrhythmogenic substrate
topic_facet Ciencias Médicas
Arrhythmias
Prediabetes
Impaired glucose tolerance
Camkii
Ryanodine receptor
description Background: Heart failure and arrhythmias occur more frequently in patients with type 2 diabetes (T2DM) than in the general population. T2DM is preceded by a prediabetic condition marked by elevated reactive oxygen species (ROS) and subclinical cardiovascular defects. Although multifunctional Ca2+ calmodulin-dependent protein kinase II (CaMKII) is ROS-activated and CaMKII hyperactivity promotes cardiac diseases, a link between prediabetes and CaMKII in the heart is unprecedented. Objectives: To prove the hypothesis that increased ROS and CaMKII activity contribute to heart failure and arrhythmogenic mechanisms in early stage diabetes. Methods–Results: Echocardiography, electrocardiography, biochemical and intracellular Ca2+ (Ca2+i) determinations were performed in fructose-rich diet-induced impaired glucose tolerance, a prediabetes model, in rodents. Fructose-rich diet rats showed decreased contractility and hypertrophy associated with increased CaMKII activity, ROS production, oxidized CaMKII and enhanced CaMKII-dependent ryanodine receptor (RyR2) phosphorylation compared to rats fed with control diet. Isolated cardiomyocytes from fructose-rich diet showed increased spontaneous Ca2+i release events associated with spontaneous contractions, which were prevented by KN-93, a CaMKII inhibitor, or addition of Tempol, a ROS scavenger, to the diet. Moreover, fructose-rich diet myocytes showed increased diastolic Ca2+ during the burst of spontaneous Ca2+i release events. Mice treated with Tempol or with sarcoplasmic reticulum-targeted CaMKII-inhibition by transgenic expression of the CaMKII inhibitory peptide AIP, were protected from fructose-rich diet-induced spontaneous Ca2+i release events, spontaneous contractions and arrhythmogenesis in vivo, despite ROS increases. Conclusions: RyR2 phosphorylation by ROS-activated CaMKII, contributes to impaired glucose tolerance-induced arrhythmogenic mechanisms, suggesting that CaMKII inhibition could prevent prediabetic cardiovascular complications and/or evolution.
format Articulo
Preprint
author Sommese, Leandro Matías
Valverde, Carlos Alfredo
Blanco, Paula Graciela
Castro, María Cecilia
Vélez Rueda, Jorge Omar
Kaetzel, Marcia
Dedman, John
Anderson, Mark E.
Mattiazzi, Ramona Alicia
Palomeque, Julieta
author_facet Sommese, Leandro Matías
Valverde, Carlos Alfredo
Blanco, Paula Graciela
Castro, María Cecilia
Vélez Rueda, Jorge Omar
Kaetzel, Marcia
Dedman, John
Anderson, Mark E.
Mattiazzi, Ramona Alicia
Palomeque, Julieta
author_sort Sommese, Leandro Matías
title Ryanodine receptor phosphorylation by CaMKII promotes spontaneous Ca2+ release events in a rodent model of early stage diabetes: The arrhythmogenic substrate
title_short Ryanodine receptor phosphorylation by CaMKII promotes spontaneous Ca2+ release events in a rodent model of early stage diabetes: The arrhythmogenic substrate
title_full Ryanodine receptor phosphorylation by CaMKII promotes spontaneous Ca2+ release events in a rodent model of early stage diabetes: The arrhythmogenic substrate
title_fullStr Ryanodine receptor phosphorylation by CaMKII promotes spontaneous Ca2+ release events in a rodent model of early stage diabetes: The arrhythmogenic substrate
title_full_unstemmed Ryanodine receptor phosphorylation by CaMKII promotes spontaneous Ca2+ release events in a rodent model of early stage diabetes: The arrhythmogenic substrate
title_sort ryanodine receptor phosphorylation by camkii promotes spontaneous ca2+ release events in a rodent model of early stage diabetes: the arrhythmogenic substrate
publishDate 2016
url http://sedici.unlp.edu.ar/handle/10915/96349
https://ri.conicet.gov.ar/11336/12294
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4872299/
work_keys_str_mv AT sommeseleandromatias ryanodinereceptorphosphorylationbycamkiipromotesspontaneousca2releaseeventsinarodentmodelofearlystagediabetesthearrhythmogenicsubstrate
AT valverdecarlosalfredo ryanodinereceptorphosphorylationbycamkiipromotesspontaneousca2releaseeventsinarodentmodelofearlystagediabetesthearrhythmogenicsubstrate
AT blancopaulagraciela ryanodinereceptorphosphorylationbycamkiipromotesspontaneousca2releaseeventsinarodentmodelofearlystagediabetesthearrhythmogenicsubstrate
AT castromariacecilia ryanodinereceptorphosphorylationbycamkiipromotesspontaneousca2releaseeventsinarodentmodelofearlystagediabetesthearrhythmogenicsubstrate
AT velezruedajorgeomar ryanodinereceptorphosphorylationbycamkiipromotesspontaneousca2releaseeventsinarodentmodelofearlystagediabetesthearrhythmogenicsubstrate
AT kaetzelmarcia ryanodinereceptorphosphorylationbycamkiipromotesspontaneousca2releaseeventsinarodentmodelofearlystagediabetesthearrhythmogenicsubstrate
AT dedmanjohn ryanodinereceptorphosphorylationbycamkiipromotesspontaneousca2releaseeventsinarodentmodelofearlystagediabetesthearrhythmogenicsubstrate
AT andersonmarke ryanodinereceptorphosphorylationbycamkiipromotesspontaneousca2releaseeventsinarodentmodelofearlystagediabetesthearrhythmogenicsubstrate
AT mattiazziramonaalicia ryanodinereceptorphosphorylationbycamkiipromotesspontaneousca2releaseeventsinarodentmodelofearlystagediabetesthearrhythmogenicsubstrate
AT palomequejulieta ryanodinereceptorphosphorylationbycamkiipromotesspontaneousca2releaseeventsinarodentmodelofearlystagediabetesthearrhythmogenicsubstrate
bdutipo_str Repositorios
_version_ 1764820492045254657

Ejemplares similares