Combined walking exercise and alkali therapy in patients with CKD4–5 regulates intramuscular free amino acid pools and ubiquitin E3 ligase expression

• Autor(a) principal: Watson, Emma L.
• Data de Publicação: 2013
• Outros Autores: Kosmadakis, George C., Smith, Alice C., Viana, Joao L., Brown, Jeremy R., Molyneux, Karen, Pawluczyk, Izabella Z. A., Mulheran, Michael, Bishop, Nicolette C., Shirreffs, Susan, Maughan, Ronald J., Owen, Paul J., John, Stephen G., McIntyre, Christopher W., Feehally, John, Bevington, Alan
• Tipo de documento: Artigo
• Idioma: eng
• Título da fonte: Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
• Texto Completo: http://hdl.handle.net/10400.24/1770
• topic: Adult; Aged; Aged, 80 and over; Amino Acids; Bicarbonates; Combined Modality Therapy; Female; Humans; Lactic Acid; Male; Middle Aged; Muscle Proteins; Muscle, Skeletal; Proto-Oncogene Proteins c-akt; Renal Insufficiency, Chronic; Tripartite Motif Proteins; Ubiquitin-Protein Ligases; Exercise Therapy; Walking

Muscle-wasting in chronic kidney disease (CKD) arises from several factors including sedentary behaviour and metabolic acidosis. Exercise is potentially beneficial but might worsen acidosis through exercise-induced lactic acidosis. We studied the chronic effects of exercise in CKD stage 4-5 patients (brisk walking, 30 min, 5 times/week), and non-exercising controls; each group receiving standard oral bicarbonate (STD), or additional bicarbonate (XS) (Total n = 26; Exercising + STD n = 9; Exercising +XS n = 6; Control + STD n = 8; Control + XS n = 3). Blood and vastus lateralis biopsies were drawn at baseline and 6 months. The rise in blood lactate in submaximal treadmill tests was suppressed in the Exercising + XS group. After 6 months, intramuscular free amino acids (including the branched chain amino acids) in the Exercising + STD group showed a striking chronic depletion. This did not occur in the Exercising + XS group. The effect in Exercising + XS patients was accompanied by reduced transcription of ubiquitin E3-ligase MuRF1 which activates proteolysis via the ubiquitin-proteasome pathway. Other anabolic indicators (Akt activation and suppression of the 14 kDa actin catabolic marker) were unaffected in Exercising + XS patients. Possibly because of this, overall suppression of myofibrillar proteolysis (3-methylhistidine output) was not observed. It is suggested that alkali effects in exercisers arose by countering exercise-induced acidosis. Whether further anabolic effects are attainable on combining alkali with enhanced exercise (e.g. resistance exercise) merits further investigation.