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dc.contributor.authorSánchez, Gina
dc.contributor.authorAraneda, Felipe
dc.contributor.authorPeña, Juan Pedro
dc.contributor.authorFinkelstein, José Pablo
dc.contributor.authorRiquelme, Jaime A.
dc.contributor.authorMontecinos, Luis
dc.contributor.authorBarrientos, Genaro
dc.contributor.authorLlanos, Paola
dc.contributor.authorPedrozo, Zully
dc.contributor.authorSaid, Matilde
dc.contributor.authorBull, Ricardo
dc.contributor.authorDonoso, Paulina
dc.description.abstractVentricular 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.es_ES
dc.sourceInternational Journal of Molecular Scienceses_ES
dc.subjectCalcium release channelses_ES
dc.subjectReactive oxygen species (ROS)es_ES
dc.subjectRedox modificationses_ES
dc.subjectVentricular tachycardiaes_ES
dc.subjectNADPH oxidasees_ES
dc.titleHigh-Fat-Diet-Induced Obesity Produces Spontaneous Ventricular Arrhythmias and Increases the Activity of Ryanodine Receptors in Micees_ES
uvm.escuelaEscuela de Ciencias Veterinariases_ES
uvm.carreraMedicina veterinariaes_ES

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