Cardioprotective Mechanism Of S-nitroso-n-acetylcysteine Via S-nitrosated Betadrenoceptor-2 In The Ldlr-/- Mice.

dc.creatorWanschel, Amarylis Claudine Bonito Azeredo
dc.creatorCaceres, Viviane Menezes
dc.creatorMoretti, Ana Iochabel Soares
dc.creatorBruni-Cardoso, Alexandre
dc.creatorde Carvalho, Hernandes Faustino
dc.creatorde Souza, Heraldo Possolo
dc.creatorLaurindo, Francisco Rafael Martins
dc.creatorSpadari, Regina Célia
dc.creatorKrieger, Marta Helena
dc.date2014-Jan
dc.date2015-11-27T13:44:02Z
dc.date2015-11-27T13:44:02Z
dc.date.accessioned2018-03-29T01:23:00Z
dc.date.available2018-03-29T01:23:00Z
dc.identifierNitric Oxide : Biology And Chemistry / Official Journal Of The Nitric Oxide Society. v. 36, p. 58-66, 2014-Jan.
dc.identifier1089-8611
dc.identifier10.1016/j.niox.2013.12.003
dc.identifierhttp://www.ncbi.nlm.nih.gov/pubmed/24333561
dc.identifierhttp://repositorio.unicamp.br/jspui/handle/REPOSIP/201982
dc.identifier24333561
dc.identifier.urihttp://repositorioslatinoamericanos.uchile.cl/handle/2250/1302215
dc.descriptionPrevious 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.
dc.description36
dc.description58-66
dc.languageeng
dc.relationNitric Oxide : Biology And Chemistry / Official Journal Of The Nitric Oxide Society
dc.relationNitric Oxide
dc.rightsfechado
dc.rightsCopyright © 2013 Elsevier Inc. All rights reserved.
dc.sourcePubMed
dc.subjectAcetylcysteine
dc.subjectAnimals
dc.subjectAntioxidants
dc.subjectApoptosis
dc.subjectDyslipidemias
dc.subjectEndoplasmic Reticulum
dc.subjectGene Expression Regulation
dc.subjectHydrogen Peroxide
dc.subjectHypertrophy, Left Ventricular
dc.subjectMale
dc.subjectMice
dc.subjectMice, Inbred C57bl
dc.subjectMice, Knockout
dc.subjectMyocytes, Cardiac
dc.subjectNitric Oxide Synthase Type Iii
dc.subjectNitrogen
dc.subjectOxidative Stress
dc.subjectReactive Oxygen Species
dc.subjectReceptors, Adrenergic, Beta-2
dc.subjectReceptors, Ldl
dc.subjectSuperoxides
dc.subjectBetadrenoceptor-2
dc.subjectHydrogen Peroxide
dc.subjectS-nitrosated
dc.subjectS-nitroso-n-acetylscysteine
dc.subjectSuperoxide
dc.subjectVentricular Hypertrophy
dc.titleCardioprotective Mechanism Of S-nitroso-n-acetylcysteine Via S-nitrosated Betadrenoceptor-2 In The Ldlr-/- Mice.
dc.typeArtículos de revistas


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