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Effects of Salmeterol on Skeletal Muscle Cells: Metabolic and Pro-Apoptotic Features.
MedLine Citation:
PMID:  21552152     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
PURPOSE.: Salmeterol is a β2-Adrenergic Receptor (β2-AR) agonist widely used for the treatment of asthma and chronic obstructive pulmonary disease (COPD). It has been shown that Salmeterol is also used at supra-therapeutic doses, as performance-enhancing substance in sport practice. Although, the abuse of β-agonists might determine some adverse effects, the molecular effects of Salmeterol on skeletal muscle cells remain unclear. METHODS.: We evaluated the effects of Salmeterol (0.1-10 μM) on both proliferative and differentiated rat L6C5 and mouse C2C12 skeletal muscle cell lines. The metabolic effects were evaluated by glyceraldehyde phosphate dehydrogenase, lactate dehydrogenase, citrate synthase, 3-OH acyl-CoA dehydrogenase, and alanine transglutaminase activities. Cytotoxic and apoptotic effect were analyzed by MTS, Trypan blue exclusion assay, TUNEL assay, western blot analysis and immunofluorescence staining. RESULTS.: We showed that Salmeterol reduced the growth rate of proliferating cells in dose and time dependent manner (6-48 hours). An increase of oxidative metabolism was found after 6 hours in C2C12 and L6C5 myoblasts and in C2C12 myotubes respect to control cells, while in L6C5 myotubes prevailed anaerobic metabolism. Exposure of myoblasts and myotubes for 48 and 72 hrs at high Salmeterol concentrations, induced apoptosis by the activation of the intrinsic apoptotic pathway, as confirmed by the modulation of the apoptotic proteins Bcl-xL, caspase-9, poly (ADP-ribose) polymerase (PARP), and by the cytoplasmic release of Smac/DIABLO. CONCLUSION.: Altogether our results demonstrate that short-term supra-therapeutic Salmeterol exposure increased oxidative metabolic pathways on skeletal muscle cells, whereas prolonged treatment inhibits cell growth and exerts either a cytostatic, or pro-apoptotic effect in a time and dose-dependent way.
Authors:
Guglielmo Duranti; Piergiorgio La Rosa; Ivan Dimauro; Francesca Wannenes; Sergio Bonini; Stefania Sabatini; Paolo Parisi; Daniela Caporossi
Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2011-5-4
Journal Detail:
Title:  Medicine and science in sports and exercise     Volume:  -     ISSN:  1530-0315     ISO Abbreviation:  -     Publication Date:  2011 May 
Date Detail:
Created Date:  2011-5-9     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  8005433     Medline TA:  Med Sci Sports Exerc     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Affiliation:
1Department of Health Sciences, University of Rome "Foro Italico", Rome, Italy, 2Institute of Translational Pharmacology (IFT) National Research Council of Italy, Rome, Italy; 3Department of Internal Medicine, Second University of Naples, Italy.
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