Moderate Treadmill Training Induces Limited Effects on Quadriceps Muscle Hypertrophy in Mice Exposed to Cigarette Smoke Involving Metalloproteinase 2

Abstract

Gracielle Vieira Ramos, 1, 2 Ivo Vieira de Sousa Neto, 3 Alessandra Choqueta Toledo-Arruda, 4, 5 Rita de Cassia Marqueti, 3 Rodolfo P Vieira, 6– 8 Milton A Martins, 5 Tânia F Salvini, 9 João Luiz Quaglioti Durigan 10 1Physical Therapy Division, University of Brasilia, Brasília, DF, Brazil; 2Department of Physical Therapy, University Paulista, Brasília, DF, Brazil; 3Laboratory of Molecular Analysis, Graduate Program of Sciences and Technology of Health, Universidade de Brasília, Brasília, DF, Brazil; 4Faculty of Physiotherapy, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil; 5Department of Medicine Clinical (LIM 20), School of Medicine, University of São Paulo, São Paulo, Brazil; 6Universidade Brasil, Post-Graduation Program in Bioengineering, São Paulo, Brazil; 7Laboratory of Pulmonary and Exercise Immunology (LABPEI), Brazilian Institute of Teaching and Research in Pulmonary and Exercise Immunology (IBEPIPE) and Nove de Julho University (UNINOVE), São Paulo, SP, Brazil; 8Federal University of Sao Paulo, Post-Graduation Program in Sciences of Human Movement and Rehabilitation, São Paulo, Brazil; 9Department of Physical Therapy, Federal University of São Carlos, São Carlos, Brazil; 10Rehabilitation Sciences Graduation Program, University of Brasilia, Brasília, DF, BrazilCorrespondence: Gracielle Vieira RamosDepartment of Physical Therapy, University Paulista, Sgas Quadra 913, s/nº - Conjunto B - Asa Sul, Brasília, DF, Brazil, 70390-130 Email [email protected]: Long-term cigarette smoke (CS) induces substantive extrapulmonary effects, including musculoskeletal system disorders. Exercise training seems to protect long-term smokers against fiber atrophy in the locomotor muscles. Nevertheless, the extracellular matrix (ECM) changes in response to aerobic training remain largely unknown. Thus, we investigated the effects of moderate treadmill training on aerobic performance, cross-sectional area (CSA), fiber distribution, and metalloproteinase 2 (MMP-2) activity on quadriceps muscle in mice exposed to chronic CS.Methods: Male mice were randomized into four groups: control or smoke (6 per group) and exercise or exercise+smoke (5 per group). Animals were exposed to 12 commercially filtered cigarettes per day (0.8 mg of nicotine, 10 mg of tar, and 10 mg of CO per cigarette). The CSA, fibers distribution, and MMP-2 activity by zymography were assessed after a period of treadmill training (50% of maximal exercise capacity for 60 min/day, 5 days/week) for 24 weeks.Results: The CS exposure did not change CSA compared to the control group (p> 0.05), but minor fibers in the frequency distribution (< 1000 μm 2) were observed. Long-term CS exposure attenuated CSA increases in exercise conditions (smoke+exercise vs exercise) while did not impair aerobic performance. Quadriceps CSA increased in mice nonsmoker submitted to aerobic training (p = 0.001). There was higher pro-MMP-2 activity in the smoke+exercise group when compared to the smoke group (p = 0.01). Regarding active MMP-2, the exercise showed higher values when compared to the control group (p = 0.001).Conclusion: Moderate treadmill training for 24 weeks in mice exposed to CS did not modify CSA, despite inducing higher pro-MMP-2 activity in the quadriceps muscle, suggesting limited effects on ECM remodeling. Our findings may contribute to new insights into molecular mechanisms for CS conditions.Keywords: physical exercise, chronic obstructive pulmonary disease, MMP-2, inflammation

Keywords

• physical exercise
• chronic obstructive pulmonary disease
• mmp-2
• inflammation.