Cardioprotective mechanism of S-nitroso-N-acetylcysteine via S-nitrosated betadrenoceptor-2 in the LDLr−/− mice
| Autor: | Viviane Caceres, Ana Iochabel Soares Moretti, Alexandre Bruni-Cardoso, Heraldo Possolo de Souza, Regina C. Spadari, Amarylis C. B. A. Wanschel, Marta Helena Krieger, Francisco R.M. Laurindo, Hernandes F. Carvalho |
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| Rok vydání: | 2014 |
| Předmět: |
Male
medicine.medical_specialty Cancer Research Nitric Oxide Synthase Type III Ventricular hypertrophy Nitrogen Physiology Clinical Biochemistry Apoptosis S-nitrosated medicine.disease_cause Left ventricular hypertrophy Endoplasmic Reticulum Biochemistry Antioxidants chemistry.chemical_compound Mice Enos Superoxides Internal medicine Betadrenoceptor-2 medicine Animals Myocytes Cardiac S-nitroso-N-acetylscysteine Dyslipidemias Mice Knockout TUNEL assay biology Chemistry Superoxide medicine.disease biology.organism_classification Hydrogen peroxide Acetylcysteine Mice Inbred C57BL Oxidative Stress Endocrinology Atheroma Gene Expression Regulation Receptors LDL Hypertrophy Left Ventricular Receptors Adrenergic beta-2 Reactive Oxygen Species Oxidative stress |
| Zdroj: | Nitric Oxide. 36:58-66 |
| ISSN: | 1089-8603 |
| DOI: | 10.1016/j.niox.2013.12.003 |
| Popis: | 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 15days 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. |
| Databáze: | OpenAIRE |
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