Please use this identifier to cite or link to this item: http://hdl.handle.net/10553/119434
Title: Post-exercise ischemia reveals the role of muscle metabolite accumulation and tissue oxygenation in autophagy activation/deactivation in human skeletal muscle
Authors: Martinez Canton, Miriam 
Gallego Sellés, Angel 
Martín Rincón, Marcos 
Pérez Valera, Mario 
Martín Rodríguez, Saúl 
Galván Álvarez, Víctor 
Morales Álamo, David 
Dorado García, Cecilia 
López Calbet, José Antonio 
UNESCO Clasification: 2415 Biología molecular
Issue Date: 2020
Project: Desarrolloy Caracterización Molecular de Un Nuevo Modelo de Precondicionamiento Remoto 
Identificacion E Integracion de Nuevos Factores Moleculares, Fisiologicosy Bioelectricos Determinantes Del Rendimiento en El Ejercicio de Sprint 
Conference: 25th Annual Congress of the European College of Sport Science (ECSS 2020) 
Abstract: Although the mechanisms by which exercise activates autophagy remain unknown, high intensity, fatigue, hypoxia and high-energy turnover could be involved. This study aimed to ascertain whether intra-muscular acidification, Pi accumulation, and low PO2 play a role in autophagy activation in human skeletal muscle. We hypothesized that autophagy would be activated depending on muscle energy levels, metabolite accumulation and PIO2. METHODS: Eleven men performed an incremental exercise to exhaustion (IE) in normoxia (Nx, PIO2:143 mmHg) and hypoxia (Hyp, PIO2:73 mmHg). At exhaustion, the circulation of one leg was instantaneously occluded (300mmHg) for 1 min. Muscle metabolites and AMPKa/ULK1/Beclin1, p62 and LC3B, were measured (Western Blot) in m. vastus lateralis biopsies, before (PRE), 10s after (POST, only occluded leg), and 1min after IE in the occluded (OC1M) and non-occluded (nOC1M) legs. Blood samples were drawn from the femoral vein and muscle tissue oxygenation measured by NIRS. Statistical analysis was performed using repeated-measures ANOVA. RESULTS: At POST, muscle PCr and ATP were decreased while Cr, lactate and H+ were increased (Nx vs Hyp, P=NS). Femoral vein PO2 was lower in Hyp (P<0.001). Occlusion reduced muscle oxygenation, impeded PCr recovery and increased acidification. The ratio pThr172/total AMPKa was increased 4.5-fold at POST, remaining elevated 3.8-fold above PRE in OC1M (both P<0.001), while it recovered close to basal in nOC1M. At POST, pSer555-ULK1 and the ratio pSer15/total Beclin1 were increased 1.6 and 2.0-fold, respectively, while LC3B was reduced by 24%. These changes were essentially maintained only in the occluded leg (OC1M vs PRE, P<0.01). The ratio LC3BII/I and p62 were reduced at POST and recovered 1min after IE in both legs. The IE elicited similar responses in signalling in Nx and Hyp. CONCLUSION: IE to exhaustion activates autophagy-signalling in human skeletal muscle with similar responses in Nx and Hyp, likely due to a similar metabolite accumulation at the end of both IEs. The increased acidification, reduction of tissue PO2 and Pi accumulation during ischemia, did not activate autophagy further. The upregulated phosphorylations were reverted to PRE values after 1-min recovery with free circulation, coinciding with better oxygenation (NIRS), and nearly a 50% recovery of PCr. Thus, Pi is likely involved in the regulation of autophagy in human skeletal muscle. After one min of recovery with free circulation, muscle lactate and H+ remained at the same level reached at exhaustion, indicating that neither high muscle lactate nor H+ seem necessary to maintain autophagy activation. Our findings demonstrate that autophagy deactivation is extremely fast in human skeletal muscle. The FIO2 during the exercise seems to play a secondary role since no additional activation of autophagy was observed at exhaustion in hypoxia compared to normoxia.
URI: http://hdl.handle.net/10553/119434
ISBN: 9783981841435
Source: 25th Annual Congress of the European College of Sport Science (ECSS 2020)
Appears in Collections:Actas de congresos
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