1. Effects of Salmeterol on Skeletal Muscle Cells
- Author
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Piergiorgio La Rosa, Sergio Bonini, Francesca Wannenes, Paolo Parisi, Stefania Sabatini, Daniela Caporossi, Ivan Dimauro, and Guglielmo Duranti
- Subjects
medicine.medical_specialty ,Smac/DIABLO ,bcl-X Protein ,Apoptosis ,Physical Therapy, Sports Therapy and Rehabilitation ,Citrate (si)-Synthase ,β-Ar agonists ,Cell Line ,Mice ,chemistry.chemical_compound ,Internal medicine ,Lactate dehydrogenase ,medicine ,Animals ,Humans ,Myocyte ,Albuterol ,Orthopedics and Sports Medicine ,Muscle, Skeletal ,Adrenergic beta-2 Receptor Agonists ,Salmeterol Xinafoate ,Glyceraldehyde 3-phosphate dehydrogenase ,Cell Proliferation ,Transglutaminases ,L-Lactate Dehydrogenase ,biology ,Cell growth ,Myogenesis ,3-Hydroxyacyl CoA Dehydrogenases ,Skeletal muscle ,Skeletal ,Caspase 9 ,Phosphoric Monoester Hydrolases ,Rats ,L6C5 ,Oxygen ,medicine.anatomical_structure ,Endocrinology ,chemistry ,Terminal deoxynucleotidyl transferase ,apoptosis ,C2C12 ,Poly(ADP-ribose) Polymerases ,biology.protein ,Muscle ,Salmeterol ,medicine.drug - Abstract
Purpose: Salmeterol is a s2-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 s-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
- Published
- 2011
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