Purpose: Salmeterol is a β 2-adrenergic receptor agonist widely used for the treatment of asthma and chronic obstructive pulmonary disease. It has been shown that salmeterol is also used at supratherapeutic 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 effects were analyzed by 3-(4,5-dimethylthiazol-1)-5-(3-carboxymeth-oxyphenyl)-2H-tetrazolium, trypan blue exclusion assay, terminal deoxynucleotidyl transferase dUTP nick end labeling assay, Western blot analysis, and immunofluorescence staining. RESULTS: We showed that salmeterol reduced the growth rate of proliferating cells in a dose-and time-dependent manner (6-48 h). An increase in oxidative metabolism was found after 6 h in C2C12 and L6C5 myoblasts and in C2C12 myotubes with respect to control cells, while in L6C5 myotubes, anaerobic metabolism prevailed. Exposure of myoblasts and myotubes for 48 and 72 h 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, and poly (ADP-ribose) polymerase and by the cytoplasmic release of Smac/DIABLO. Conclusions: Altogether, our results demonstrate that short-term supratherapeutic salmeterol exposure increased oxidative metabolic pathways on skeletal muscle cells, whereas prolonged treatment inhibits cell growth and exerts either a cytostatic or a proapoptotic effect in a time-and dose-dependent way. © 2011 by the American College of Sports Medicine.
Effects of salmeterol on skeletal muscle cells: Metabolic and proapoptotic features / Duranti, G.; La Rosa, P.; Dimauro, I.; Wannenes, F.; Bonini, S.; Sabatini, S.; Parisi, P.; Caporossi, D.. - In: MEDICINE AND SCIENCE IN SPORTS AND EXERCISE. - ISSN 0195-9131. - 43:12(2011), pp. 2259-2273. [10.1249/MSS.0b013e3182223094]
|Titolo:||Effects of salmeterol on skeletal muscle cells: Metabolic and proapoptotic features|
|Data di pubblicazione:||2011|
|Citazione:||Effects of salmeterol on skeletal muscle cells: Metabolic and proapoptotic features / Duranti, G.; La Rosa, P.; Dimauro, I.; Wannenes, F.; Bonini, S.; Sabatini, S.; Parisi, P.; Caporossi, D.. - In: MEDICINE AND SCIENCE IN SPORTS AND EXERCISE. - ISSN 0195-9131. - 43:12(2011), pp. 2259-2273. [10.1249/MSS.0b013e3182223094]|
|Appartiene alla tipologia:||01a Articolo in rivista|
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