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1.
FASEB J ; 35(12): e22010, 2021 12.
Artículo en Inglés | MEDLINE | ID: mdl-34724256

RESUMEN

The hypoxia-inducible nuclear-encoded mitochondrial protein NADH dehydrogenase (ubiquinone) 1 alpha subcomplex, 4-like 2 (NDUFA4L2) has been demonstrated to decrease oxidative phosphorylation and production of reactive oxygen species in neonatal cardiomyocytes, brain tissue and hypoxic domains of cancer cells. Prolonged local hypoxia can negatively affect skeletal muscle size and tissue oxidative capacity. Although skeletal muscle is a mitochondrial rich, oxygen sensitive tissue, the role of NDUFA4L2 in skeletal muscle has not previously been investigated. Here we ectopically expressed NDUFA4L2 in mouse skeletal muscles using adenovirus-mediated expression and in vivo electroporation. Moreover, femoral artery ligation (FAL) was used as a model of peripheral vascular disease to induce hind limb ischemia and muscle damage. Ectopic NDUFA4L2 expression resulted in reduced mitochondrial respiration and reactive oxygen species followed by lowered AMP, ADP, ATP, and NAD+ levels without affecting the overall protein content of the mitochondrial electron transport chain. Furthermore, ectopically expressed NDUFA4L2 caused a ~20% reduction in muscle mass that resulted in weaker muscles. The loss of muscle mass was associated with increased gene expression of atrogenes MurF1 and Mul1, and apoptotic genes caspase 3 and Bax. Finally, we showed that NDUFA4L2 was induced by FAL and that the Ndufa4l2 mRNA expression correlated with the reduced capacity of the muscle to generate force after the ischemic insult. These results show, for the first time, that mitochondrial NDUFA4L2 is a novel regulator of skeletal muscle mass and force. Specifically, induced NDUFA4L2 reduces mitochondrial activity leading to lower levels of important intramuscular metabolites, including adenine nucleotides and NAD+ , which are hallmarks of mitochondrial dysfunction and hence shows that dysfunctional mitochondrial activity may drive muscle wasting.


Asunto(s)
Complejo I de Transporte de Electrón/metabolismo , Hipoxia/fisiopatología , Mitocondrias/metabolismo , Músculo Esquelético/patología , Atrofia Muscular/patología , Animales , Proliferación Celular , Complejo I de Transporte de Electrón/genética , Femenino , Ratones , Ratones Endogámicos C57BL , Músculo Esquelético/metabolismo , Atrofia Muscular/metabolismo , Especies Reactivas de Oxígeno
2.
Eur J Appl Physiol ; 122(2): 459-474, 2022 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-34799752

RESUMEN

PURPOSE: Traditional high-intensity interval exercise (HIIE) highly stimulates the cardiorespiratory system and increases energy expenditure (EE) during exercise. High-intensity resistance exercise (HIRE) has become more popular in recreationally active subjects. The physiological responses to HIRE performed with light or moderate load is currently largely unknown. Here, we examined the effect of the type of interval exercise [HIRE at 40% (HIRE40) and 60% (HIRE60) 1-RM vs. traditional HIIE] on the cardiorespiratory response and EE during and after exercise. METHODS: Fifteen recreationally active adults randomly completed traditional HIIE on an ergocyle, HIRE40 and HIRE60. The sessions consisted of two sets of ten 30-s intervals (power at 100% VO2max during HIIE; maximal number of repetitions for 10 different free-weight exercises during HIRE40 and HIRE60) separated by 30-s active recovery periods. Gas exchange, heart rate (HR) and EE were assessed during and after exercise. RESULTS: VO2mean, VO2peak, HRmean, the time spent above 90% VO2max and HRmax, and aerobic EE were lower in both HIRE sessions compared with HIIE (P < 0.05). Anaerobic glycolytic contribution to total exercise EE was higher in HIRE40 and HIRE60 compared with HIIE (P < 0.001). EE from excess post-exercise oxygen consumption (EPOC) was similar after the three sessions. Overall, similar cardiorespiratory responses and EE were found in HIRE40 and HIRE60. CONCLUSIONS: HIRE is not as effective as HIIE for increasing the cardiorespiratory response and EE during exercise, while EPOC remains similar in HIRE and HIIE. These parameters are not substantially different between HIRE40 and HIRE60.


Asunto(s)
Capacidad Cardiovascular/fisiología , Metabolismo Energético/fisiología , Entrenamiento de Intervalos de Alta Intensidad/métodos , Esfuerzo Físico/fisiología , Entrenamiento de Fuerza/métodos , Estudios Cruzados , Prueba de Esfuerzo , Femenino , Frecuencia Cardíaca/fisiología , Humanos , Masculino , Consumo de Oxígeno/fisiología , Intercambio Gaseoso Pulmonar/fisiología , Adulto Joven
3.
Eur J Appl Physiol ; 122(1): 255-266, 2022 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-34674024

RESUMEN

PURPOSE: Unaccustomed eccentric contractions generally result in a long-lasting contractile impairment, referred to as prolonged low-frequency force depression (PLFFD), and delayed-onset muscle soreness (DOMS). We here used repeated drop jumps (DJs) as an eccentric contraction model and studied the effects of increasing the time between DJs from 20 s to 5 min. We hypothesized that both PLFFD and DOMS would be less marked at the longer DJ interval due to the longer time to restore structural elements between DJs. METHODS: Young men (n = 12) randomly performed 50 DJs with either 20-s (DJ-20 s) or 5-min (DJ-5 min) rest between DJs. Voluntary, 20 Hz and 100 Hz electrically stimulated isometric knee extension torques and muscle soreness were monitored before and for 7 days after DJs; serum CK activity was measured to assess muscle fibre protein leakage. In additional experiments, changes in mRNA levels were assessed in muscle biopsies collected before and 1 h after exercise. RESULTS: A marked PLFFD was observed with both protocols and the extent of 20 Hz torque depression was smaller immediately and 1 day after DJ-5 min than after DJ-20 s (p < 0.05), whereas the MVC and 100 Hz torques were similarly decreased with the two protocols. Markedly larger differences between the two protocols were observed for the muscle soreness score, which 1-4 days after exercise was about two times larger with DJ-20 s than with DJ-5 min (p < 0.01). CONCLUSIONS: The larger protective effect of the longer DJ interval against DOMS than against PLFFD indicates that their underlying mechanisms involve different structural elements.


Asunto(s)
Rodilla/fisiología , Contracción Muscular/fisiología , Mialgia/prevención & control , Descanso , Adulto , Biomarcadores/sangre , Biopsia con Aguja , Creatina Quinasa/sangre , Estimulación Eléctrica , Humanos , Masculino , Dimensión del Dolor , Factores de Tiempo , Torque , Adulto Joven
4.
Eur J Appl Physiol ; 121(4): 1219-1232, 2021 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-33564963

RESUMEN

PURPOSE: Carbohydrate (CHO) restriction could be a potent metabolic regulator of endurance exercise-induced muscle adaptations. Here, we determined whether post-exercise CHO restriction following strenuous exercise combining continuous cycling exercise (CCE) and sprint interval exercise could affect the gene expression related to mitochondrial biogenesis and oxidative metabolism in human skeletal muscle. METHODS: In a randomized cross-over design, 8 recreationally active males performed two cycling exercise sessions separated by 4 weeks. Each session consisted of 60-min CCE and six 30-s all-out sprints, which was followed by ingestion of either a CHO or placebo beverage in the post-exercise recovery period. Muscle glycogen concentration and the mRNA levels of several genes related to mitochondrial biogenesis and oxidative metabolism were determined before, immediately after, and at 3 h after exercise. RESULTS: Compared to pre-exercise, strenuous cycling led to a severe muscle glycogen depletion (> 90%) and induced a large increase in PGC1A and PDK4 mRNA levels (~ 20-fold and ~ 10-fold, respectively) during the acute recovery period in both trials. The abundance of the other transcripts was not changed or was only moderately increased during this period. CHO restriction during the 3-h post-exercise period blunted muscle glycogen resynthesis but did not increase the mRNA levels of genes associated with muscle adaptation to endurance exercise, as compared with abundant post-exercise CHO consumption. CONCLUSION: CHO restriction after a glycogen-depleting and metabolically-demanding cycling session is not effective for increasing the acute mRNA levels of genes involved in mitochondrial biogenesis and oxidative metabolism in human skeletal muscle.


Asunto(s)
Carbohidratos de la Dieta/farmacología , Músculo Esquelético/metabolismo , Biogénesis de Organelos , Acondicionamiento Físico Humano/métodos , Adulto , Dieta Baja en Carbohidratos/efectos adversos , Dieta Baja en Carbohidratos/métodos , Carbohidratos de la Dieta/administración & dosificación , Glucógeno/metabolismo , Humanos , Masculino , Mitocondrias Musculares/metabolismo , Músculo Esquelético/efectos de los fármacos , Músculo Esquelético/fisiología , Coactivador 1-alfa del Receptor Activado por Proliferadores de Peroxisomas gamma/genética , Coactivador 1-alfa del Receptor Activado por Proliferadores de Peroxisomas gamma/metabolismo , Acondicionamiento Físico Humano/efectos adversos , Piruvato Deshidrogenasa Quinasa Acetil-Transferidora/genética , Piruvato Deshidrogenasa Quinasa Acetil-Transferidora/metabolismo
5.
Scand J Med Sci Sports ; 30(6): 998-1007, 2020 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-32187403

RESUMEN

Prolonged low-frequency force depression (PLFFD) induced by fatiguing exercise is characterized by a persistent depression in submaximal contractile force during the recovery period. Muscle glycogen depletion is known to limit physical performance during prolonged low- and moderate-intensity exercise, and accelerating glycogen resynthesis with post-exercise carbohydrate intake can facilitate recovery and improve repeated bout exercise performance. Short-term, high-intensity exercise, however, can cause PLFFD without any marked decrease in glycogen. Here, we studied whether recovery from PLFFD was accelerated by carbohydrate ingestion after 60 minutes of moderate-intensity glycogen-depleting cycling exercise followed by six 30-seconds all-out cycling sprints. We used a randomized crossover study design where nine recreationally active males drank a beverage containing either carbohydrate or placebo after exercise. Blood glucose and muscle glycogen concentrations were determined at baseline, immediately post-exercise, and during the 3-hours recovery period. Transcutaneous electrical stimulation of the quadriceps muscle was performed to determine the extent of PLFFD by eliciting low-frequency (20 Hz) and high-frequency (100 Hz) stimulations. Muscle glycogen was severely depleted after exercise, with a significantly higher rate of muscle glycogen resynthesis during the 3-hours recovery period in the carbohydrate than in the placebo trials (13.7 and 5.4 mmol glucosyl units/kg wet weight/h, respectively). Torque at 20 Hz was significantly more depressed than 100 Hz torque during the recovery period in both conditions, and the extent of PLFFD (20/100 Hz ratio) was not different between the two trials. In conclusion, carbohydrate supplementation enhances glycogen resynthesis after glycogen-depleting exercise but does not improve force recovery when the exercise also involves all-out cycling sprints.


Asunto(s)
Glucemia/metabolismo , Carbohidratos de la Dieta/administración & dosificación , Ejercicio Físico , Glucógeno/metabolismo , Contracción Muscular , Músculo Esquelético/metabolismo , Adolescente , Adulto , Bebidas , Estudios Cruzados , Humanos , Masculino , Músculo Cuádriceps , Adulto Joven
6.
Am J Physiol Cell Physiol ; 317(1): C101-C110, 2019 07 01.
Artículo en Inglés | MEDLINE | ID: mdl-30917033

RESUMEN

The specific impact of reduced temperature on skeletal muscle adaptation has been poorly investigated. Cold water immersion, one situation leading to decreased skeletal muscle temperature, is commonly proposed to reduce the perception of fatigue and muscle soreness after strenuous exercise. In contrast, it may impair long-term benefits of resistance exercise training on muscle strength and hypertrophy. To date, the physiological factors responsible for this blunted muscle adaptation remain unclear. Here, we used a cell culture model of human primary myotubes to specifically investigate the intrinsic behavior of muscle cells during mild hypothermia (MH). Newly formed myotubes were exposed to either 37°C or 32°C to evaluate the effect of MH on myotube size and morphology, protein synthesis, and anabolic signaling. We also compared the glutamine (GLUT)-induced hypertrophic response between myotubes incubated at 32°C or 37°C. We showed that 48 h exposure to MH altered the cellular morphology (greater myotube area, shorter myosegments, myotubes with irregular shape) and impaired GLUT-induced myotube hypertrophy. Moreover, MH specifically reduced protein synthesis at 8 h. This result may be explained by an altered regulation of ribosome biogenesis, as evidenced by a lower expression of 45S pre-ribosomal RNA and MYC protein, and a lower total RNA concentration. Furthermore, MH blunted GLUT-induced increase in protein synthesis at 8 h, a finding consistent with an impaired activation of the mechanistic target of rapamycin pathway. In conclusion, this study demonstrates that MH impairs the morphology of human myotubes and alters the hypertrophic response to GLUT.


Asunto(s)
Forma de la Célula/efectos de los fármacos , Frío/efectos adversos , Glutamina/farmacología , Fibras Musculares Esqueléticas/efectos de los fármacos , Adulto , Tamaño de la Célula , Células Cultivadas , Femenino , Humanos , Hipertrofia , Masculino , Fibras Musculares Esqueléticas/metabolismo , Fibras Musculares Esqueléticas/patología , Cultivo Primario de Células , Proteínas Proto-Oncogénicas c-myc/genética , Proteínas Proto-Oncogénicas c-myc/metabolismo , ARN Ribosómico/genética , ARN Ribosómico/metabolismo , Transducción de Señal , Serina-Treonina Quinasas TOR/metabolismo , Factores de Tiempo
7.
J Physiol ; 597(12): 3133-3146, 2019 06.
Artículo en Inglés | MEDLINE | ID: mdl-31074054

RESUMEN

KEY POINTS: How defects in muscle contractile function contribute to weakness in amyotrophic lateral sclerosis (ALS) were systematically investigated. Weakness in whole muscles from late stage SOD1G93A mice was explained by muscle atrophy as seen by reduced mass and maximal force. On the other hand, surviving single muscle fibres in late stage SOD1G93A have preserved intracellular Ca2+ handling, normal force-generating capacity and increased fatigue resistance. These intriguing findings provide a substrate for therapeutic interventions to potentiate muscular capacity and delay the progression of the ALS phenotype. ABSTRACT: Amyotrophic lateral sclerosis (ALS) is a motor neuron disease characterized by degeneration and loss of motor neurons, leading to severe muscle weakness and paralysis. The SOD1G93A mouse model of ALS displays motor neuron degeneration and a phenotype consistent with human ALS. The purpose of this study was to determine whether muscle weakness in ALS can be attributed to impaired intrinsic force generation in skeletal muscles. In the current study, motor neuron loss and decreased force were evident in whole flexor digitorum brevis (FDB) muscles of mice in the late stage of disease (125-150 days of age). However, in intact single muscle fibres, specific force, tetanic myoplasmic free [Ca2+ ] ([Ca2+ ]i ), and resting [Ca2+ ]i remained unchanged with disease. Fibre-type distribution was maintained in late-stage SOD1G93A FDB muscles, but remaining muscle fibres displayed greater fatigue resistance compared to control and showed increased expression of myoglobin and mitochondrial respiratory chain proteins that are important determinants of fatigue resistance. Expression of genes central to both mitochondrial biogenesis and muscle atrophy where increased, suggesting that atrophic and compensatory adaptive signalling occurs simultaneously within the muscle tissue. These results support the hypothesis that muscle weakness in SOD1G93A is primarily attributed to neuromuscular degeneration and not intrinsic muscle fibre defects. In fact, surviving muscle fibres displayed maintained adaptive capacity with an exercise training-like phenotype, which suggests that compensatory mechanisms are activated that can function to delay disease progression.


Asunto(s)
Esclerosis Amiotrófica Lateral/fisiopatología , Fibras Musculares Esqueléticas/fisiología , Adaptación Fisiológica , Esclerosis Amiotrófica Lateral/patología , Animales , Calcio/fisiología , Modelos Animales de Enfermedad , Femenino , Masculino , Ratones Endogámicos C57BL , Neuronas Motoras/patología , Neuronas Motoras/fisiología , Debilidad Muscular , Degeneración Nerviosa
8.
J Physiol ; 595(24): 7413-7426, 2017 12 15.
Artículo en Inglés | MEDLINE | ID: mdl-28980321

RESUMEN

KEY POINTS: We investigated whether intramuscular temperature affects the acute recovery of exercise performance following fatigue-induced by endurance exercise. Mean power output was better preserved during an all-out arm-cycling exercise following a 2 h recovery period in which the upper arms were warmed to an intramuscular temperature of Ì´ 38°C than when they were cooled to as low as 15°C, which suggested that recovery of exercise performance in humans is dependent on muscle temperature. Mechanisms underlying the temperature-dependent effect on recovery were studied in intact single mouse muscle fibres where we found that recovery of submaximal force and restoration of fatigue resistance was worsened by cooling (16-26°C) and improved by heating (36°C). Isolated whole mouse muscle experiments confirmed that cooling impaired muscle glycogen resynthesis. We conclude that skeletal muscle recovery from fatigue-induced by endurance exercise is impaired by cooling and improved by heating, due to changes in glycogen resynthesis rate. ABSTRACT: Manipulation of muscle temperature is believed to improve post-exercise recovery, with cooling being especially popular among athletes. However, it is unclear whether such temperature manipulations actually have positive effects. Accordingly, we studied the effect of muscle temperature on the acute recovery of force and fatigue resistance after endurance exercise. One hour of moderate-intensity arm cycling exercise in humans was followed by 2 h recovery in which the upper arms were either heated to 38°C, not treated (33°C), or cooled to ∼15°C. Fatigue resistance after the recovery period was assessed by performing 3 × 5 min sessions of all-out arm cycling at physiological temperature for all conditions (i.e. not heated or cooled). Power output during the all-out exercise was better maintained when muscles were heated during recovery, whereas cooling had the opposite effect. Mechanisms underlying the temperature-dependent effect on recovery were tested in mouse intact single muscle fibres, which were exposed to ∼12 min of glycogen-depleting fatiguing stimulation (350 ms tetani given at 10 s interval until force decreased to 30% of the starting force). Fibres were subsequently exposed to the same fatiguing stimulation protocol after 1-2 h of recovery at 16-36°C. Recovery of submaximal force (30 Hz), the tetanic myoplasmic free [Ca2+ ] (measured with the fluorescent indicator indo-1), and fatigue resistance were all impaired by cooling (16-26°C) and improved by heating (36°C). In addition, glycogen resynthesis was faster at 36°C than 26°C in whole flexor digitorum brevis muscles. We conclude that recovery from exhaustive endurance exercise is accelerated by raising and slowed by lowering muscle temperature.


Asunto(s)
Ejercicio Físico , Hipertermia Inducida/métodos , Hipotermia Inducida/efectos adversos , Contracción Muscular , Músculo Esquelético/fisiología , Recuperación de la Función , Adulto , Animales , Calcio/metabolismo , Células Cultivadas , Femenino , Glucógeno/metabolismo , Humanos , Hipertermia Inducida/efectos adversos , Hipotermia Inducida/métodos , Masculino , Ratones , Ratones Endogámicos C57BL , Fatiga Muscular , Músculo Esquelético/metabolismo
9.
FASEB J ; 30(12): 3929-3941, 2016 12.
Artículo en Inglés | MEDLINE | ID: mdl-27601440

RESUMEN

Reduced oxygen (O2) levels (hypoxia) are present during embryogenesis and exposure to altitude and in pathologic conditions. During embryogenesis, myogenic progenitor cells reside in a hypoxic microenvironment, which may regulate their activity. Satellite cells are myogenic progenitor cells localized in a local environment, suggesting that the O2 level could affect their activity during muscle regeneration. In this review, we present the idea that O2 levels regulate myogenesis and muscle regeneration, we elucidate the molecular mechanisms underlying myogenesis and muscle regeneration in hypoxia and depict therapeutic strategies using changes in O2 levels to promote muscle regeneration. Severe hypoxia (≤1% O2) appears detrimental for myogenic differentiation in vitro, whereas a 3-6% O2 level could promote myogenesis. Hypoxia impairs the regenerative capacity of injured muscles. Although it remains to be explored, hypoxia may contribute to the muscle damage observed in patients with pathologies associated with hypoxia (chronic obstructive pulmonary disease, and peripheral arterial disease). Hypoxia affects satellite cell activity and myogenesis through mechanisms dependent and independent of hypoxia-inducible factor-1α. Finally, hyperbaric oxygen therapy and transplantation of hypoxia-conditioned myoblasts are beneficial procedures to enhance muscle regeneration in animals. These therapies may be clinically relevant to treatment of patients with severe muscle damage.-Chaillou, T. Lanner, J. T. Regulation of myogenesis and skeletal muscle regeneration: effects of oxygen levels on satellite cell activity.


Asunto(s)
Diferenciación Celular/efectos de los fármacos , Desarrollo de Músculos/efectos de los fármacos , Músculo Esquelético/metabolismo , Oxígeno , Regeneración/efectos de los fármacos , Células Satélite del Músculo Esquelético/efectos de los fármacos , Animales , Diferenciación Celular/fisiología , Humanos , Desarrollo de Músculos/fisiología , Oxígeno/metabolismo , Oxígeno/farmacología , Regeneración/fisiología , Células Satélite del Músculo Esquelético/metabolismo
10.
J Cell Physiol ; 231(9): 1894-902, 2016 09.
Artículo en Inglés | MEDLINE | ID: mdl-26684695

RESUMEN

The ribosome has historically been considered to have no cell-specific function but rather serve in a "housekeeping" capacity. This view is being challenged by evidence showing that heterogeneity in the protein composition of the ribosome can lead to the functional specialization of the ribosome. Expression profiling of different tissues revealed that ribosomal protein large 3-like (Rpl3l) is exclusively expressed in striated muscle. In response to a hypertrophic stimulus, Rpl3l expression in skeletal muscle was significantly decreased by 82% whereas expression of the ubiquitous paralog Rpl3 was significantly increased by ∼fivefold. Based on these findings, we developed the hypothesis that Rpl3l functions as a negative regulator of muscle growth. To test this hypothesis, we used the Tet-On system to express Rpl3l in myoblasts during myotube formation. In support of our hypothesis, RPL3L expression significantly impaired myotube growth as assessed by myotube diameter (-23%) and protein content (-14%). Further analysis showed that the basis of this impairment was caused by a significant decrease in myoblast fusion as the fusion index was significantly lower (-17%) with RPL3L expression. These findings are the first evidence to support the novel concept of ribosome specialization in skeletal muscle and its role in the regulation of skeletal muscle growth. J. Cell. Physiol. 231: 1894-1902, 2016. © 2015 Wiley Periodicals, Inc.


Asunto(s)
Desarrollo de Músculos/fisiología , Fibras Musculares Esqueléticas/metabolismo , Músculo Esquelético/metabolismo , Mioblastos/metabolismo , Proteínas Ribosómicas/metabolismo , Animales , Diferenciación Celular/fisiología , Masculino , Ratones Endogámicos C57BL , Fibras Musculares Esqueléticas/citología , Proteína Ribosomal L3
12.
J Cell Physiol ; 229(11): 1584-94, 2014 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-24604615

RESUMEN

The ribosome is a supramolecular ribonucleoprotein complex that functions at the heart of the translation machinery to convert mRNA into protein. Ribosome biogenesis is the primary determinant of translational capacity of the cell and accordingly has an essential role in the control of cell growth in eukaryotes. Cumulative evidence supports the hypothesis that ribosome biogenesis has an important role in the regulation of skeletal muscle mass. The purpose of this review is to, first, summarize the main mechanisms known to regulate ribosome biogenesis and, second, put forth the hypothesis that ribosome biogenesis is a central mechanism used by skeletal muscle to regulate protein synthesis and control skeletal muscle mass in response to anabolic and catabolic stimuli. The mTORC1 and Wnt/ß-catenin/c-myc signaling pathways are discussed as the major pathways that work in concert with each of the three RNA polymerases (RNA Pol I, II, and III) in regulating ribosome biogenesis. Consistent with our hypothesis, activation of these two pathways has been shown to be associated with ribosome biogenesis during skeletal muscle hypertrophy. Although further study is required, the finding that ribosome biogenesis is altered under catabolic states, in particular during disuse atrophy, suggests that its activation represents a novel therapeutic target to reduce or prevent muscle atrophy. Lastly, the emerging field of ribosome specialization is discussed and its potential role in the regulation of gene expression during periods of skeletal muscle plasticity.


Asunto(s)
Músculo Esquelético/anatomía & histología , Músculo Esquelético/metabolismo , Ribosomas/metabolismo , Animales , Humanos , Tamaño de los Órganos , Transducción de Señal
14.
Mol Cell Biochem ; 390(1-2): 31-40, 2014 May.
Artículo en Inglés | MEDLINE | ID: mdl-24385110

RESUMEN

Hypoxia impairs the muscle fibre-type shift from fast-to-slow during post-natal development; however, this adaptation could be a consequence of the reduced voluntary physical activity associated with hypoxia exposure rather than the result of hypoxia per se. Moreover, muscle oxidative capacity could be reduced in hypoxia, particularly when hypoxia is combined with additional stress. Here, we used a model of muscle regeneration to mimic the fast-to-slow fibre-type conversion observed during post-natal development. We hypothesised that hypoxia would impair the recovery of the myosin heavy chain (MHC) profile and oxidative capacity during muscle regeneration. To test this hypothesis, the soleus muscle of female rats was injured by notexin and allowed to recover for 3, 7, 14 and 28 days under normoxia or hypobaric hypoxia (5,500 m altitude) conditions. Ambient hypoxia did not impair the recovery of the slow MHC profile during muscle regeneration. However, hypoxia moderately decreased the oxidative capacity (assessed from the activity of citrate synthase) of intact muscle and delayed its recovery in regenerated muscle. Hypoxia transiently increased in both regenerated and intact muscles the content of phosphorylated AMPK and Pgc-1α mRNA, two regulators involved in mitochondrial biogenesis, while it transiently increased in intact muscle the mRNA level of the mitophagic factor BNIP3. In conclusion, hypoxia does not act to impair the fast-to-slow MHC isoform transition during regeneration. Hypoxia alters the oxidative capacity of intact muscle and delays its recovery in regenerated muscle; however, this adaptation to hypoxia was independent of the studied regulators of mitochondrial turn-over.


Asunto(s)
Hipoxia de la Célula/fisiología , Fibras Musculares de Contracción Lenta/fisiología , Músculo Esquelético/crecimiento & desarrollo , Regeneración , Animales , Femenino , Proteínas de la Membrana/metabolismo , Proteínas Mitocondriales/metabolismo , Fibras Musculares de Contracción Lenta/metabolismo , Músculo Esquelético/metabolismo , Cadenas Pesadas de Miosina/metabolismo , Fenotipo , Ratas , Ratas Wistar
15.
Front Physiol ; 15: 1356488, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38476145

RESUMEN

Background: We investigated the impact of 1) passive heating (PH) induced by single and intermittent/prolonged hot-water immersion (HWI) and 2) the duration of PH, on muscle contractile function under the unfatigued state, and during the development of muscle fatigue. Methods: Twelve young males volunteered for this study consisting of two phases: single phase (SP) followed by intermittent/prolonged phase (IPP), with both phases including two conditions (i.e., four trials in total) performed randomly: control passive sitting (CON) and HWI (44-45°C; water up to the waist level). SP-HWI included one continuous 45-min bath (from 15 to 60 min). IPP-HWI included an initial 45-min bath (from 15 to 60 min) followed by eight additional 15-min baths interspaced with 15-min breaks at room temperature between 75 and 300 min. Intramuscular (Tmu; measured in the vastus lateralis muscle) and rectal (Trec) temperatures were determined. Neuromuscular testing (performed in the knee extensors and flexors) was performed at baseline and 60 min later during SP, and at baseline, 60, 90, 150 and 300 min after baseline during IPP. A fatiguing protocol (100 electrical stimulations of the knee extensors) was performed after the last neuromuscular testing of each trial. Results: HWI increased Tmu and Trec to 38°C-38.5°C (p < 0.05) during both SP and IPP. Under the unfatigued state, HWI did not affect electrically induced torques at 20 Hz (P20) and 100 Hz (P100). However, it induced a shift towards a faster contractile profile during both SP and IPP, as evidenced by a decreased P20/P100 ratio (p < 0.05) and an improved muscle relaxation (i.e., reduced half-relaxation time and increased rate of torque relaxation; p < 0.05). Despite a reduced voluntary activation (i.e., -2.63% ± 4.19% after SP-HWI and -5.73% ± 4.31% after IPP-HWI; condition effect: p < 0.001), HWI did not impair maximal isokinetic and isometric contraction torques. During the fatiguing protocol, fatigue index and the changes in muscle contractile properties were larger after HWI than CON conditions (p < 0.05). Finally, none of these parameters were significantly affected by the heating duration. Conclusion: PH induces changes in muscle contractile function which are not augmented by prolonged exposure when thermal stress is moderate.

16.
Front Aging ; 4: 1171850, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37256189

RESUMEN

Age-related loss of skeletal muscle mass leads to a reduction of strength. It is likely due to an inadequate stimulation of muscle protein synthesis (MPS) in response to anabolic stimuli, such as mechanical load. Ribosome biogenesis is a major determinant of translational capacity and is essential for the control of muscle mass. This mini-review aims to put forth the hypothesis that ribosome biogenesis is impaired by aging in response to mechanical load, which could contribute to the age-related anabolic resistance and progressive muscle atrophy. Recent animal studies indicate that aging impedes muscle hypertrophic response to mechanical overload. This is associated with an impaired transcription of ribosomal DNA (rDNA) by RNA polymerase I (Pol I), a limited increase in total RNA concentration, a blunted activation of AKT/mTOR pathway, and an increased phosphorylation of AMPK. In contrast, an age-mediated impairment of ribosome biogenesis is unlikely in response to electrical stimulations. In human, the hypertrophic response to resistance exercise training is diminished with age. This is accompanied by a deficit in long-term MPS and an absence of increased total RNA concentration. The results addressing the acute response to resistance exercise suggest an impaired Pol I-mediated rDNA transcription and attenuated activation/expression of several upstream regulators of ribosome biogenesis in muscles from aged individuals. Altogether, emerging evidence indicates that impaired ribosome biogenesis could partly explain age-related anabolic resistance to mechanical load, which may ultimately contribute to progressive muscle atrophy. Future research should develop more advanced molecular tools to provide in-depth analysis of muscle ribosome biogenesis.

17.
Front Physiol ; 14: 1172817, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37025384

RESUMEN

Background: We investigated the impact of moderate muscle cooling induced by single and intermittent/prolonged cold-water immersions (CWI) on muscle force and contractility in unfatigued state and during the development of fatigue resulting from electrically induced contractions. Methods: Twelve young males participated in this study consisting of two phases [single phase (SP) followed by intermittent/prolonged phase (IPP)], with both phases including two conditions (i.e., four trials in total) performed randomly: control passive sitting (CON) and cold-water immersions (10°C). SP-CWI included one 45 min-bath (from 15 to 60 min). IPP-CWI included three baths (45 min-bath from 15 to 60 min, and 15 min-baths from 165 to 180 min and from 255 to 270 min), with participants sitting at room temperature the rest of the time until 300 min. Blood pressure and intramuscular (Tmu) temperature were assessed, and neuromuscular testing was performed at baseline and 60 min after baseline during SP, and at baseline, 60, 90, 150 and 300 min after baseline during IPP. A fatiguing protocol (100 electrical stimulations) was performed after the last neuromuscular testing of each trial. Results: In unfatigued state, SP-CWI and IPP-CWI reduced electrically induced torque at 100 Hz (P100) but not at 20 Hz (P20), and increased P20/P100 ratio. The changes from baseline for P100 and P20/P100 ratio were lower in IPP-CWI than SP-CWI. Both cold-water immersion conditions slowed down muscle contraction and relaxation, and reduced maximal isokinetic contraction torque, but the changes from baseline were lower after IPP-CWI than SP-CWI. cold-water immersions did not impair maximal voluntary isometric contraction. During the fatiguing protocol, torque fatigue index and the changes in muscle contractile properties were larger after IPP-CWI than SP-CWI, but were in the same range as after CON conditions. The differences of muscle contractile function between SP-CWI and IPP-CWI were accompanied by a lower reduction of superficial Tmu and a smaller increase in systolic blood pressure after IPP-CWI than SP-CWI. Conclusion: IPP-CWI induces a less pronounced fast-to-slow contractile transition compared to SP-CWI, and this may result from the reduced vasoconstriction response and enhanced blood perfusion of the superficial muscle vessels, which could ultimately limit the reduction of superficial Tmu.

19.
Am J Physiol Regul Integr Comp Physiol ; 302(5): R643-54, 2012 Mar 01.
Artículo en Inglés | MEDLINE | ID: mdl-22189670

RESUMEN

Hypoxia induces a loss of skeletal muscle mass, but the signaling pathways and molecular mechanisms involved remain poorly understood. We hypothesized that hypoxia could impair skeletal muscle hypertrophy induced by functional overload (Ov). To test this hypothesis, plantaris muscles were overloaded during 5, 12, and 56 days in female rats exposed to hypobaric hypoxia (5,500 m), and then, we examined the responses of specific signaling pathways involved in protein synthesis (Akt/mTOR) and breakdown (atrogenes). Hypoxia minimized the Ov-induced hypertrophy at days 5 and 12 but did not affect the hypertrophic response measured at day 56. Hypoxia early reduced the phosphorylation levels of mTOR and its downstream targets P70(S6K) and rpS6, but it did not affect the phosphorylation levels of Akt and 4E-BP1, in Ov muscles. The role played by specific inhibitors of mTOR, such as AMPK and hypoxia-induced factors (i.e., REDD1 and BNIP-3) was studied. REDD1 protein levels were reduced by overload and were not affected by hypoxia in Ov muscles, whereas AMPK was not activated by hypoxia. Although hypoxia significantly increased BNIP-3 mRNA levels at day 5, protein levels remained unaffected. The mRNA levels of the two atrogenes MURF1 and MAFbx were early increased by hypoxia in Ov muscles. In conclusion, hypoxia induced a transient alteration of muscle growth in this hypertrophic model, at least partly due to a specific impairment of the mTOR/P70(S6K) pathway, independently of Akt, by an undefined mechanism, and increased transcript levels for MURF1 and MAFbx that could contribute to stimulate the proteasomal proteolysis.


Asunto(s)
Hipoxia/fisiopatología , Músculo Esquelético/patología , Músculo Esquelético/fisiopatología , Transducción de Señal/fisiología , Soporte de Peso/fisiología , Animales , Femenino , Hipertrofia , Hipoxia/metabolismo , Modelos Animales , Proteínas Musculares/metabolismo , Músculo Esquelético/metabolismo , Proteolisis , Proteínas Proto-Oncogénicas c-akt/metabolismo , Ratas , Ratas Wistar , Proteínas Quinasas S6 Ribosómicas 70-kDa/metabolismo , Proteínas Ligasas SKP Cullina F-box/metabolismo , Serina-Treonina Quinasas TOR/metabolismo , Proteínas de Motivos Tripartitos , Ubiquitina-Proteína Ligasas/metabolismo
20.
Sports Med Open ; 8(1): 37, 2022 Mar 07.
Artículo en Inglés | MEDLINE | ID: mdl-35254558

RESUMEN

The application of post-exercise cooling (e.g., cold water immersion) and post-exercise heating has become a popular intervention which is assumed to increase functional recovery and may improve chronic training adaptations. However, the effectiveness of such post-exercise temperature manipulations remains uncertain. The aim of this comprehensive review was to analyze the effects of post-exercise cooling and post-exercise heating on neuromuscular function (maximal strength and power), fatigue resistance, exercise performance, and training adaptations. We focused on three exercise types (resistance, endurance and sprint exercises) and included studies investigating (1) the early recovery phase, (2) the late recovery phase, and (3) repeated application of the treatment. We identified that the primary benefit of cooling was in the early recovery phase (< 1 h post-exercise) in improving fatigue resistance in hot ambient conditions following endurance exercise and possibly enhancing the recovery of maximal strength following resistance exercise. The primary negative impact of cooling was with chronic exposure which impaired strength adaptations and decreased fatigue resistance following resistance training intervention (12 weeks and 4-12 weeks, respectively). In the early recovery phase, cooling could also impair sprint performance following sprint exercise and could possibly reduce neuromuscular function immediately after endurance exercise. Generally, no benefits of acute cooling were observed during the 24-72-h recovery period following resistance and endurance exercises, while it could have some benefits on the recovery of neuromuscular function during the 24-48-h recovery period following sprint exercise. Most studies indicated that chronic cooling does not affect endurance training adaptations following 4-6 week training intervention. We identified limited data employing heating as a recovery intervention, but some indications suggest promise in its application to endurance and sprint exercise.

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