Document Detail

Exercise and tachycardia increase NADPH oxidase and ryanodine receptor-2 activity: possible role in cardioprotection.
MedLine Citation:
PMID:  18006481     Owner:  NLM     Status:  MEDLINE    
AIM: Our objective was to investigate in cardiac muscle the contribution of NADPH oxidase to (a) ryanodine receptor-2 (RyR2) S-glutathionylation and (b) the preconditioning effects of exercise and tachycardia on infarct size following coronary artery occlusion. METHODS AND RESULTS: We measured NADPH oxidase activity, RyR2 S-glutathionylation, and calcium release kinetics in sarcoplasmic reticulum (SR) vesicles isolated from dog ventricular muscle after exercise and tachycardia, plus or minus prior administration of the NADPH oxidase inhibitor apocynin. In ventricular muscle sections, we studied the colocalization of NADPH oxidase and RyR2 by confocal microscopy using fluorescent antibodies. We determined the effect of apocynin on the infarct size produced by occlusion of the descendent anterior coronary artery in animals preconditioned by exercise or tachycardia. Exercise and tachycardia increased NADPH oxidase activity, RyR2 S-glutathionylation, and calcium release rates in isolated SR vesicles. Cardiac muscle sections displayed significant colocalization of NADPH oxidase and RyR2, suggesting direct and specific effects of reactive oxygen species (ROS) produced by NADPH oxidase on RyR2 activation. The NADPH oxidase inhibitor apocynin prevented the increase in RyR2 S-glutathionylation, reduced calcium release activity, and completely prevented the protective effects of exercise and tachycardia on infarct size. CONCLUSIONS: The loss of cardioprotection induced by the NADPH oxidase inhibitor suggests that ROS generated by this enzyme are important mediators of the preconditioning response, which presumably involves NADPH oxidase-induced RyR2 S-glutathionylation.
Gina Sánchez; Matías Escobar; Zully Pedrozo; Pilar Macho; Raúl Domenech; Steffen Härtel; Cecilia Hidalgo; Paulina Donoso
Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2007-09-18
Journal Detail:
Title:  Cardiovascular research     Volume:  77     ISSN:  0008-6363     ISO Abbreviation:  Cardiovasc. Res.     Publication Date:  2008 Jan 
Date Detail:
Created Date:  2008-01-28     Completed Date:  2008-08-26     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  0077427     Medline TA:  Cardiovasc Res     Country:  Netherlands    
Other Details:
Languages:  eng     Pagination:  380-6     Citation Subset:  IM    
Programa de Fisiopatología, Instituto de Ciencias Biomédicas y Centro FONDAP de Estudios Moleculares de la Célula, Facultad de Medicina, Universidad de Chile, Chile.
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MeSH Terms
Acetophenones / pharmacology
Calcium / metabolism
Glutathione / metabolism
Ischemic Preconditioning, Myocardial*
NADPH Oxidase / metabolism*
Physical Conditioning, Animal*
Reactive Oxygen Species / metabolism
Ryanodine Receptor Calcium Release Channel / physiology*
Sarcoplasmic Reticulum / metabolism
Tachycardia / metabolism*
Reg. No./Substance:
0/Acetophenones; 0/Reactive Oxygen Species; 0/Ryanodine Receptor Calcium Release Channel; 498-02-2/acetovanillone; 70-18-8/Glutathione; 7440-70-2/Calcium; EC Oxidase

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