RESUMEN
We tested whether aerobic exercise training (AET) would modulate the skeletal muscle protein quality control (PQC) in a model of chronic kidney disease (CKD) in rats. Adult Wistar rats were evaluated in four groups: control (CS) or trained (CE), and 5/6 nephrectomy sedentary (5/6NxS) or trained (5/6NxE). Exercised rats were submitted to treadmill exercise (60 min., five times/wk for 2 months). We evaluated motor performance (tolerance to exercise on the treadmill and rotarod), cross-sectional area (CSA), gene and protein levels related to the unfolded protein response (UPR), protein synthesis/survive and apoptosis signalling, accumulated misfolded proteins, chymotrypsin-like proteasome activity (UPS activity), redox balance and heat-shock protein (HSP) levels in the tibialis anterior. 5/6NxS presented a trend towards to atrophy, with a reduction in motor performance, down-regulation of protein synthesis and up-regulation of apoptosis signalling; increases in UPS activity, misfolded proteins, GRP78, derlin, HSP27 and HSP70 protein levels, ATF4 and GRP78 genes; and increase in oxidative damage compared to CS group. In 5/6NxE, we observed a restoration in exercise tolerance, accumulated misfolded proteins, UPS activity, protein synthesis/apoptosis signalling, derlin, HSPs protein levels as well as increase in ATF4, GRP78 genes and ATF6α protein levels accompanied by a decrease in oxidative damage and increased catalase and glutathione peroxidase activities. The results suggest a disruption of PQC in white muscle fibres of CKD rats previous to the atrophy. AET can rescue this disruption for the UPR, prevent accumulated misfolded proteins and reduce oxidative damage, HSPs protein levels and exercise tolerance.
Asunto(s)
Actividad Motora/fisiología , Atrofia Muscular/prevención & control , Condicionamiento Físico Animal , Biosíntesis de Proteínas , Insuficiencia Renal Crónica/terapia , Factor de Transcripción Activador 4/genética , Factor de Transcripción Activador 4/metabolismo , Factor de Transcripción Activador 6/genética , Factor de Transcripción Activador 6/metabolismo , Animales , Catalasa/genética , Catalasa/metabolismo , Modelos Animales de Enfermedad , Regulación de la Expresión Génica , Glutatión Peroxidasa/genética , Glutatión Peroxidasa/metabolismo , Proteínas de Choque Térmico/genética , Proteínas de Choque Térmico/metabolismo , Pruebas de Función Renal , Masculino , Músculo Esquelético/metabolismo , Músculo Esquelético/fisiopatología , Atrofia Muscular/genética , Atrofia Muscular/metabolismo , Atrofia Muscular/fisiopatología , Nefrectomía/métodos , Complejo de la Endopetidasa Proteasomal/metabolismo , Ratas , Ratas Wistar , Insuficiencia Renal Crónica/genética , Insuficiencia Renal Crónica/fisiopatología , Insuficiencia Renal Crónica/cirugía , Prueba de Desempeño de Rotación con Aceleración Constante , Conducta Sedentaria , Transducción de SeñalRESUMEN
Aerobic exercise training (AET) induces several skeletal muscle changes, improving aerobic exercise capacity and health. Conversely, to the positive effects of AET, the cachexia syndrome is characterized by skeletal muscle wasting. Cachexia is a multifactorial disorderassociated with other chronic diseases such as heart failure and cancer. In these diseases, an overactivation of ubiquitin-proteasome and autophagy systems associated with a reduction in protein synthesis culminates in severe skeletal muscle wasting and, in the last instance, patient's death. In contrast, AET may recycle and enhance many protein expression and enzyme activities, counteracting metabolism impairment and muscle atrophy. Therefore, the aim of the current review was to discuss the supposed therapeutic effects of AET on skeletal muscle wasting in both cardiac and cancer cachexia.
Asunto(s)
Caquexia/complicaciones , Caquexia/terapia , Terapia por Ejercicio , Insuficiencia Cardíaca/complicaciones , Enfermedades Musculares/complicaciones , Enfermedades Musculares/terapia , Neoplasias/complicaciones , Animales , Caquexia/metabolismo , Ejercicio Físico , Terapia por Ejercicio/métodos , Insuficiencia Cardíaca/metabolismo , Humanos , Atrofia Muscular/complicaciones , Atrofia Muscular/metabolismo , Atrofia Muscular/terapia , Enfermedades Musculares/metabolismo , Neoplasias/metabolismo , Complejo de la Endopetidasa Proteasomal/metabolismoRESUMEN
BACKGROUND: We previously reported that exercise training (ET) facilitates the clearance of damaged proteins in heart failure. Here, we characterized the impact of ET on cardiac protein quality control during compensated ventricular hypertrophy in spontaneously hypertensive rats (SHR). METHODS AND RESULTS: SHR were randomly assigned into sedentary and swimming-trained groups. Sedentary SHR displayed cardiac hypertrophy with preserved ventricular function compared to normotensive rats, characterizing a compensated cardiac hypertrophy. Hypertensive rats presented signs of cardiac oxidative stress, depicted by increased lipid peroxidation. However, these changes were not followed by accumulation of lipid peroxidation-generated reactive aldehydes and damaged proteins. This scenario was explained, at least in part, by the increased catalytic activity of both aldehyde dehydrogenase 2 (ALDH2) and proteasome. Of interest, ET exacerbated cardiac hypertrophy, improved ventricular function, induced resting bradycardia, and decreased blood pressure in SHR. These changes were accompanied by reduced cardiac oxidative stress and a consequent decrease in ALDH2 and proteasome activities, without affecting small chaperones levels and apoptosis in SHR. CONCLUSION: Increased cardiac ALDH2 and proteasomal activities counteract the deleterious effect of excessive oxidative stress in hypertension-induced compensated cardiac hypertrophy in rats. ET has a positive effect in reducing cardiac oxidative stress without affecting protein quality control.