Please use this identifier to cite or link to this item:
Type: Artigo de periódico
Title: Cardioprotective Mechanism Of S-nitroso-n-acetylcysteine Via S-nitrosated Betadrenoceptor-2 In The Ldlr-/- Mice.
Author: Wanschel, Amarylis Claudine Bonito Azeredo
Caceres, Viviane Menezes
Moretti, Ana Iochabel Soares
Bruni-Cardoso, Alexandre
de Carvalho, Hernandes Faustino
de Souza, Heraldo Possolo
Laurindo, Francisco Rafael Martins
Spadari, Regina Célia
Krieger, Marta Helena
Abstract: Previous studies from our group have demonstrated the protective effect of S-nitroso-N-acetylcysteine (SNAC) on the cardiovascular system in dyslipidemic LDLr-/- mice that develop atheroma and left ventricular hypertrophy after 15 days on a high fat diet. We have shown that SNAC treatment attenuates plaque development via the suppression of vascular oxidative stress and protects the heart from structural and functional myocardial alterations, such as heart arrhythmia, by reducing cardiomyocyte sensitivity to catecholamines. Here we investigate the ability of SNAC to modulate oxidative stress and cell survival in cardiomyocytes during remodeling and correlation with β₂-AR signaling in mediating this protection. Ventricular superoxide (O₂⁻) and hydrogen peroxide (H₂O₂) generation was measured by HPLC methods to allow quantification of dihydroethidium (DHE) products. Ventricular histological sections were stained using terminal dUTP nick-end labeling (TUNEL) to identify nuclei with DNA degradation (apoptosis) and this was confirmed by Western blot for cleaved caspase-3 and caspase-7 protein expression. The findings show that O₂⁻ and H₂O₂ production and also cell apoptosis were increased during left ventricular hypertrophy (LVH). SNAC treatment reduced oxidative stress during on cardiac remodeling, measured by decreased H₂O₂ and O₂⁻ production (65% and 52%, respectively), and a decrease in the ratio of p-Ser1177 eNOS/total eNOS. Left ventricle (LV) from SNAC-treated mice revealed a 4-fold increase in β₂-AR expression associated with coupling change to Gi; β₂-ARs-S-nitrosation (β₂-AR-SNO) increased 61%, while apoptosis decreased by 70%. These results suggest that the cardio-protective effect of SNAC treatment is primarily through its anti-oxidant role and is associated with β₂-ARs overexpression and β₂-AR-SNO via an anti-apoptotic pathway.
Subject: Acetylcysteine
Endoplasmic Reticulum
Gene Expression Regulation
Hydrogen Peroxide
Hypertrophy, Left Ventricular
Mice, Inbred C57bl
Mice, Knockout
Myocytes, Cardiac
Nitric Oxide Synthase Type Iii
Oxidative Stress
Reactive Oxygen Species
Receptors, Adrenergic, Beta-2
Receptors, Ldl
Hydrogen Peroxide
Ventricular Hypertrophy
Citation: Nitric Oxide : Biology And Chemistry / Official Journal Of The Nitric Oxide Society. v. 36, p. 58-66, 2014-Jan.
Rights: fechado
Identifier DOI: 10.1016/j.niox.2013.12.003
Date Issue: 2014
Appears in Collections:Unicamp - Artigos e Outros Documentos

Files in This Item:
File SizeFormat 
pmed_24333561.pdf1.24 MBAdobe PDFView/Open

Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.