CaMKII activation in early diabetic hearts induces altered sarcoplasmic reticulum‑mitochondria signaling

Prediabetic myocardium, induced by fructose-rich diet (FRD), is prone to increased sarcoplasmic reticulum (SR)-Ca2+ leak and arrhythmias due to increased activity of the Ca2+/ calmodulin protein kinase II (CaMKII). However, little is known about the role of SR-mitochondria microdomains, mitochondria...

Descripción completa

Detalles Bibliográficos
Autores principales: Federico, Marilén, Zavala, Maite Raquel, Vico, Tamara, López, Sofía, Portiansky, Enrique Leo, Alvarez, Silvia, Villa Abrille, María Celeste, Palomeque, Julieta
Formato: Articulo
Lenguaje:Inglés
Publicado: 2021
Materias:
Ciencias Médicas
Cardiovascular biology
Physiology
Acceso en línea:http://sedici.unlp.edu.ar/handle/10915/130028
Aporte de:
SEDICI (UNLP) de Universidad Nacional de La Plata
id I19-R120-10915-130028
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
Cardiovascular biology
Physiology
spellingShingle Ciencias Médicas
Cardiovascular biology
Physiology
Federico, Marilén
Zavala, Maite Raquel
Vico, Tamara
López, Sofía
Portiansky, Enrique Leo
Alvarez, Silvia
Villa Abrille, María Celeste
Palomeque, Julieta
CaMKII activation in early diabetic hearts induces altered sarcoplasmic reticulum‑mitochondria signaling
topic_facet Ciencias Médicas
Cardiovascular biology
Physiology
description Prediabetic myocardium, induced by fructose-rich diet (FRD), is prone to increased sarcoplasmic reticulum (SR)-Ca2+ leak and arrhythmias due to increased activity of the Ca2+/ calmodulin protein kinase II (CaMKII). However, little is known about the role of SR-mitochondria microdomains, mitochondrial structure, and mitochondrial metabolisms. To address this knowledge gap we measured SR-mitochondrial proximity, intracellular Ca2+, and mitochondrial metabolism in wild type (WT) and AC3-I transgenic mice, with myocardial-targeted CaMKII inhibition, fed with control diet (CD) or with FRD. Confocal images showed significantly increased spontaneous Ca2+ release events in FRD vs. CD WT cardiomyocytes. [ 3H]-Ryanodine binding assay revealed higher [ 3H]Ry binding in FRD than CD WT hearts. O2 consumption at State 4 and hydrogen peroxide ( H2O2) production rate were increased, while respiratory control rate (RCR) and Ca2+ retention capacity (CRC) were decreased in FRD vs. CD WT isolated mitochondria. Transmission Electron Microscopy (TEM) images showed increased proximity at the SR-mitochondria microdomains, associated with increased tethering proteins, Mfn2, Grp75, and VDAC in FRD vs. CD WT. Mitochondria diameter was decrease and roundness and density were increased in FRD vs. CD WT specimens. The fission protein, Drp1 was significantly increased while the fusion protein, Opa1 was unchanged in FRD vs. CD WT hearts. These differences were prevented in AC3-I mice. We conclude that SR-mitochondria microdomains are subject to CaMKII-dependent remodeling, involving SR-Ca2+ leak and mitochondria fission, in prediabetic mice induced by FRD. We speculate that CaMKII hyperactivity induces SR-Ca2+ leak by RyR2 activation which in turn increases mitochondria Ca2+ content due to the enhanced SR-mitochondria tethering, decreasing CRC.
format Articulo
Articulo
author Federico, Marilén
Zavala, Maite Raquel
Vico, Tamara
López, Sofía
Portiansky, Enrique Leo
Alvarez, Silvia
Villa Abrille, María Celeste
Palomeque, Julieta
author_facet Federico, Marilén
Zavala, Maite Raquel
Vico, Tamara
López, Sofía
Portiansky, Enrique Leo
Alvarez, Silvia
Villa Abrille, María Celeste
Palomeque, Julieta
author_sort Federico, Marilén
title CaMKII activation in early diabetic hearts induces altered sarcoplasmic reticulum‑mitochondria signaling
title_short CaMKII activation in early diabetic hearts induces altered sarcoplasmic reticulum‑mitochondria signaling
title_full CaMKII activation in early diabetic hearts induces altered sarcoplasmic reticulum‑mitochondria signaling
title_fullStr CaMKII activation in early diabetic hearts induces altered sarcoplasmic reticulum‑mitochondria signaling
title_full_unstemmed CaMKII activation in early diabetic hearts induces altered sarcoplasmic reticulum‑mitochondria signaling
title_sort camkii activation in early diabetic hearts induces altered sarcoplasmic reticulum‑mitochondria signaling
publishDate 2021
url http://sedici.unlp.edu.ar/handle/10915/130028
work_keys_str_mv AT federicomarilen camkiiactivationinearlydiabeticheartsinducesalteredsarcoplasmicreticulummitochondriasignaling
AT zavalamaiteraquel camkiiactivationinearlydiabeticheartsinducesalteredsarcoplasmicreticulummitochondriasignaling
AT vicotamara camkiiactivationinearlydiabeticheartsinducesalteredsarcoplasmicreticulummitochondriasignaling
AT lopezsofia camkiiactivationinearlydiabeticheartsinducesalteredsarcoplasmicreticulummitochondriasignaling
AT portianskyenriqueleo camkiiactivationinearlydiabeticheartsinducesalteredsarcoplasmicreticulummitochondriasignaling
AT alvarezsilvia camkiiactivationinearlydiabeticheartsinducesalteredsarcoplasmicreticulummitochondriasignaling
AT villaabrillemariaceleste camkiiactivationinearlydiabeticheartsinducesalteredsarcoplasmicreticulummitochondriasignaling
AT palomequejulieta camkiiactivationinearlydiabeticheartsinducesalteredsarcoplasmicreticulummitochondriasignaling
bdutipo_str Repositorios
_version_ 1764820452965875713

Ejemplares similares