PMID- 24333561
OWN - NLM
STAT- MEDLINE
DCOM- 20140904
LR  - 20161020
IS  - 1089-8611 (Electronic)
IS  - 1089-8603 (Linking)
VI  - 36
DP  - 2014 Jan 30
TI  - Cardioprotective mechanism of S-nitroso-N-acetylcysteine via S-nitrosated 
      betadrenoceptor-2 in the LDLr-/- mice.
PG  - 58-66
LID - S1089-8603(13)00342-X [pii]
LID - 10.1016/j.niox.2013.12.003 [doi]
AB  - 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 beta(2)-AR signaling in 
      mediating this protection. Ventricular superoxide (O(2)(-)) and hydrogen peroxide 
      (H(2)O(2)) 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 O(2)(-) and H(2)O(2) 
      production and also cell apoptosis were increased during left ventricular 
      hypertrophy (LVH). SNAC treatment reduced oxidative stress during on cardiac 
      remodeling, measured by decreased H(2)O(2) and O(2)(-) 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 beta(2)-AR 
      expression associated with coupling change to Gi; beta(2)-ARs-S-nitrosation 
      (beta(2)-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 beta(2)-ARs overexpression and beta(2)-AR-SNO 
      via an anti-apoptotic pathway.
CI  - Copyright (c) 2013 Elsevier Inc. All rights reserved.
FAU - Wanschel, Amarylis Claudine Bonito Azeredo
AU  - Wanschel AC
AD  - Marc and Ruti Bell Vascular Biology and Disease Program, Leon H. Charney Division 
      of Cardiology, Department of Medicine, New York University School of Medicine, 
      New York, NY, USA; Department of Anatomy, Cellular Biology and Physiology, State 
      University of Campinas (UNICAMP), Biology Institute, Sao Paulo, Brazil. 
      Electronic address: amarylisclaudine.wanschel@nyumc.org.
FAU - Caceres, Viviane Menezes
AU  - Caceres VM
AD  - Department of Biosciences, Federal University of Sao Paulo (UNIFESP), Sao Paulo, 
      Brazil.
FAU - Moretti, Ana Iochabel Soares
AU  - Moretti AI
AD  - Department of Emergency Medicine, University of Sao Paulo (USP), Sao Paulo, 
      Brazil.
FAU - Bruni-Cardoso, Alexandre
AU  - Bruni-Cardoso A
AD  - Department of Anatomy, Cellular Biology and Physiology, State University of 
      Campinas (UNICAMP), Biology Institute, Sao Paulo, Brazil.
FAU - de Carvalho, Hernandes Faustino
AU  - de Carvalho HF
AD  - Department of Anatomy, Cellular Biology and Physiology, State University of 
      Campinas (UNICAMP), Biology Institute, Sao Paulo, Brazil.
FAU - de Souza, Heraldo Possolo
AU  - de Souza HP
AD  - Department of Emergency Medicine, University of Sao Paulo (USP), Sao Paulo, 
      Brazil.
FAU - Laurindo, Francisco Rafael Martins
AU  - Laurindo FR
AD  - Heart Institute (InCor), University of Sao Paulo School of Medicine, Sao Paulo, 
      Brazil.
FAU - Spadari, Regina Celia
AU  - Spadari RC
AD  - Department of Biosciences, Federal University of Sao Paulo (UNIFESP), Sao Paulo, 
      Brazil.
FAU - Krieger, Marta Helena
AU  - Krieger MH
AD  - Department of Anatomy, Cellular Biology and Physiology, State University of 
      Campinas (UNICAMP), Biology Institute, Sao Paulo, Brazil.
LA  - eng
PT  - Journal Article
DEP - 20131212
PL  - United States
TA  - Nitric Oxide
JT  - Nitric oxide : biology and chemistry
JID - 9709307
RN  - 0 (Antioxidants)
RN  - 0 (Reactive Oxygen Species)
RN  - 0 (Receptors, Adrenergic, beta-2)
RN  - 0 (Receptors, LDL)
RN  - 11062-77-4 (Superoxides)
RN  - 56577-02-7 (S-nitroso-N-acetylcysteine)
RN  - BBX060AN9V (Hydrogen Peroxide)
RN  - EC 1.14.13.39 (Nitric Oxide Synthase Type III)
RN  - EC 1.14.13.39 (Nos3 protein, mouse)
RN  - N762921K75 (Nitrogen)
RN  - WYQ7N0BPYC (Acetylcysteine)
SB  - IM
MH  - Acetylcysteine/*analogs & derivatives/pharmacology
MH  - Animals
MH  - Antioxidants/pharmacology
MH  - Apoptosis
MH  - Dyslipidemias
MH  - Endoplasmic Reticulum/metabolism
MH  - *Gene Expression Regulation
MH  - Hydrogen Peroxide/chemistry
MH  - Hypertrophy, Left Ventricular
MH  - Male
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Mice, Knockout
MH  - Myocytes, Cardiac/cytology
MH  - Nitric Oxide Synthase Type III/metabolism
MH  - Nitrogen/*metabolism
MH  - Oxidative Stress
MH  - Reactive Oxygen Species/metabolism
MH  - Receptors, Adrenergic, beta-2/*genetics
MH  - Receptors, LDL/*genetics
MH  - Superoxides
OTO - NOTNLM
OT  - Betadrenoceptor-2
OT  - Hydrogen peroxide
OT  - S-nitrosated
OT  - S-nitroso-N-acetylscysteine
OT  - Superoxide
OT  - Ventricular hypertrophy
EDAT- 2013/12/18 06:00
MHDA- 2014/09/05 06:00
CRDT- 2013/12/17 06:00
PHST- 2013/07/12 00:00 [received]
PHST- 2013/10/16 00:00 [revised]
PHST- 2013/12/05 00:00 [accepted]
PHST- 2013/12/17 06:00 [entrez]
PHST- 2013/12/18 06:00 [pubmed]
PHST- 2014/09/05 06:00 [medline]
AID - S1089-8603(13)00342-X [pii]
AID - 10.1016/j.niox.2013.12.003 [doi]
PST - ppublish
SO  - Nitric Oxide. 2014 Jan 30;36:58-66. doi: 10.1016/j.niox.2013.12.003. Epub 2013 
      Dec 12.