Implication des calpaïnes lors d'un remodelage musculaire induit par un traitement chronique au clenbutérol

To fight doping in an effective manner, it is essential to understand the mechanisms leading to muscle remodeling. For this purpose we analyzed the effects of clenbuterol, on muscle remodeling and various associated signaling pathways. We were particularly interested with the calpain system which has often been associated with muscle remodeling phenomena, mainly in models of atrophy. We have shown that an early calpain system solicitation during chronic treatment with clenbuterol in rats was associated with a phenotypic conversion in the Soleus and EDL muscles and hypertrophy in the EDL muscle. We then inhibited the activity of calpains with a parallel clenbuterol treatment. The muscles with a reduced activity of calpain and treated with clenbuterol did not develop muscle remodeling. These initial results reinforce the idea of an involvement of calpain in the muscle remodeling induced by chronic treatment with clenbuterol.Afin de lutter efficacement contre les malversations du dopage, il apparaît essentiel de comprendre les mécanismes conduisant au remodelage musculaire. Dans ce but nous avons analysé les effets d’un β2-agoniste, le clenbutérol, sur le remodelage musculaire et les différentes voies de signalisation qui y sont associées. Nous nous sommes particulièrement intéressés au système des calpaïnes qui a souvent été associé à des phénomènes de remodelage musculaire, principalement dans des modèles d’atrophie. Nous avons montré une sollicitation précoce du système des calpaïnes lors d’un traitement chronique au clenbutérol chez le rat associé à une conversion phénotypique dans les muscles EDL et Soléaire et à une hypertrophie dans le muscle EDL uniquement. Puis, nous avons inhibé l’activité des calpaïnes en parallèle d’un traitement au clenbutérol. Les muscles ayant une activité des calpaïnes diminuée et soumis à un traitement au clenbutérol n’ont pas développé de remodelage musculaire. Ces premiers résultats renforcent l’idée d’une implication des calpaïnes dans le remodelage musculaire induit par un traitement chronique au clenbutérol

Implication of the ubiquitous calpains during a chronic clenbuterol-dependant muscle remodelling.

Afin de lutter efficacement contre les malversations du dopage, il apparaît essentiel de comprendre les mécanismes conduisant au remodelage musculaire. Dans ce but nous avons analysé les effets d’un β2-agoniste, le clenbutérol, sur le remodelage musculaire et les différentes voies de signalisation qui y sont associées. Nous nous sommes particulièrement intéressés au système des calpaïnes qui a souvent été associé à des phénomènes de remodelage musculaire, principalement dans des modèles d’atrophie. Nous avons montré une sollicitation précoce du système des calpaïnes lors d’un traitement chronique au clenbutérol chez le rat associé à une conversion phénotypique dans les muscles EDL et Soléaire et à une hypertrophie dans le muscle EDL uniquement. Puis, nous avons inhibé l’activité des calpaïnes en parallèle d’un traitement au clenbutérol. Les muscles ayant une activité des calpaïnes diminuée et soumis à un traitement au clenbutérol n’ont pas développé de remodelage musculaire. Ces premiers résultats renforcent l’idée d’une implication des calpaïnes dans le remodelage musculaire induit par un traitement chronique au clenbutérol.To fight doping in an effective manner, it is essential to understand the mechanisms leading to muscle remodeling. For this purpose we analyzed the effects of clenbuterol, on muscle remodeling and various associated signaling pathways. We were particularly interested with the calpain system which has often been associated with muscle remodeling phenomena, mainly in models of atrophy. We have shown that an early calpain system solicitation during chronic treatment with clenbuterol in rats was associated with a phenotypic conversion in the Soleus and EDL muscles and hypertrophy in the EDL muscle. We then inhibited the activity of calpains with a parallel clenbuterol treatment. The muscles with a reduced activity of calpain and treated with clenbuterol did not develop muscle remodeling. These initial results reinforce the idea of an involvement of calpain in the muscle remodeling induced by chronic treatment with clenbuterol

Propriétés spectroscopiques des polyphénols. III - Les complexes entre l'aluminium et les polyphénols

National audienc

Early activation of rat skeletal muscle IL-6/STAT1/STAT3 dependent gene expression in resistance exercise linked to hypertrophy

Cytokine interleukin-6 (IL-6) is an essential regulator of satellite cell-mediated hypertrophic muscle growth through the transcription factor signal transducer and activator of transcription 3 (STAT3). The importance of this pathway linked to the modulation of myogenic regulatory factors expression in rat skeletal muscle undergoing hypertrophy following resistance exercise, has not been investigated. In this study, the phosphorylation and nuclear localization of STAT3, together with IL-6/STAT3-responsive gene expression, were measured after both a single bout of resistance exercise and 10 weeks of training. Flexor Digitorum Profundus muscle samples from Wistar rats were obtained 2 and 6 hours after a single bout of resistance exercise and 72 h after the last bout of either 2, 4, or 10 weeks of resistance training. We observed an increase in IL-6 and SOCS3 mRNAs concomitant with phosphorylation of STAT1 and STAT3 after 2 and 6 hours of a single bout of exercise (p<0.05). STAT3-dependent early responsive genes such as CyclinD1 and cMyc were also upregulated whereas MyoD and Myf5 mRNAs were downregulated (p<0.05). BrdU-positive satellite cells increased at 2 and 6 hours after exercise (p<0.05). Muscle fiber hypertrophy reached up to 100% after 10 weeks of training and the mRNA expression of Myf5, c-Myc and Cyclin-D1 decreased, whereas IL-6 mRNA remained upregulated. We conclude that the IL-6/STAT1/STAT3 signaling pathway and its responsive genes after a single bout of resistance exercise are an important event regulating the SC pool and behavior involved in muscle hypertrophy after ten weeks of training in rat skeletal muscle

Time course in calpain activity and autolysis in slow and fast skeletal muscle during clenbuterol treatment

Corresponding author : e-mail: [email protected] audienceCalpains are Ca2+ cysteine proteases that have been proposed to be involved in the cytoskeletal remodeling and wasting of skeletal muscle. Cumulative evidence also suggests that b2-agonists can lead to skeletal muscle hypertrophy through a mechanism probably related to calcium-dependent proteolytic enzyme. The aim of our study was to monitor calpain activity as a function of clenbuterol treatment in both slow and fast phenotype rat muscles. For this purpose, for 21 days we followed the time course of the calpain activity and of the ubiquitous calpain 1 and 2 autolysis, as well as muscle remodeling in the extensor digitorum longus (EDL) and soleus muscles of male Wistar rats treated daily with clenbuterol (4 mg_kg–1). A slow to fast fiber shift was observed in both the EDL and soleus muscles after 9 days of treatment, while hypertrophy was observed only in EDL after 9 days of treatment. Soleus muscle but not EDL muscle underwent an early apoptonecrosis phase characterized by hematoxylin and eosin staining. Total calpain activity was increased in both the EDL and soleus muscles of rats treated with clenbuterol. Moreover, calpain 1 autolysis increased significantly after 14 days in the EDL, but not in the soleus. Calpain 2 autolysis increased significantly in both muscles 6 hours after the first clenbuterol injection, indicating that clenbuterol-induced calpain 2 autolysis occurred earlier than calpain 1 autolysis. Together, these data suggest a preferential involvement of calpain 2 autolysis compared with calpain 1 autolysis in the mechanisms underlying the clenbuterol-induced skeletal muscle remodeling

Modelling training response in elite female gymnasts and optimal strategies of overload training and taper

The aim of the study is the modelling of training responses with a variable dose-response model in a sport discipline that requires highly complex coordination. We propose a method to optimise the training programme plan using the potential maximal performance gain associated with overload and tapering periods. Data from five female elite gymnasts were collected over a 3-month training period. The relationship between training amounts and performance was then assessed with a non-linear model. The optimal magnitude of training load reduction and its duration were investigated with and without an overload period using simulation procedures based on individual responses to training. The correlation between actual and modelled performances was significant (R-2=0.81 +/- 0.02, P<0.01). The standard error was 2.7%. Simulations revealed that taper preceded by an overload period allows a higher performance to be achieved compared to an absence of overload period (106.3 +/- 0.3% vs. 105.1 +/- 0.3%). With respect to the pre-taper load, the model predicts that optimal load reductions during taper were 48.4 +/- 0.7% and 42.5 +/- 1.0% for overloading and non-overloading strategies, respectively. Moreover, optimal durations of the taper period were 34 +/- 0.5 days and 22 +/- 0.5 days for overloading and non-overloading strategies, respectively. In conclusion, the study showed that the variable dose-response model describes precisely the training response in gymnasts

Calpastatin overexpression in the skeletal muscle of mice prevents clenbuterol-induced muscle hypertrophy and phenotypic shift

Contact: [email protected] audienceAccumulating evidence suggests that the calpain/calpastatin system is involved in skeletal muscle remodelling induced by beta 2-adrenoceptor agonist treatment. In addition to other pathways, the Akt/mammalian target of rapamycin (mTOR) pathway, controlling protein synthesis, and the calcium/calmodulin-dependent protein kinase 2 (CamK2) and AMP-activated protein kinase (AMPK) pathways, recently identified as calpain substrates, could be relevant in beta 2-adrenoceptor agonist-induced skeletal muscle remodelling. In the present study we investigated muscle hypertrophy and phenotypic shifts, as well as the molecular response of components of the Akt/mTOR pathway (i.e. Akt, eukaryotic initiation factor 4E-binding protein 1 (4E-BP1), ribosomal protein S6 (rpS6), CamK2 and AMPK), in response to calpastatin overexpression in the skeletal muscle of mice treated with 1mg/kg per day clenbuterol for 21days. Using gene electrotransfer of a calpastatin expression vector into the tibialis anterior of adult mice, we found that calpastatin overexpression attenuates muscle hypertrophy and phenotypic shifts induced by clenbuterol treatment. At the molecular level, calpastatin overexpression markedly decreased calpain activity, but was ineffective in altering the phosphorylation of Akt, 4E-BP1 and rpS6. In contrast, calpastatin overexpression increased the protein expression of both total AMPK and total CamK2. In conclusion, the results support the contention that the calpain/calpastatin system plays a crucial role in skeletal muscle hypertrophy and phenotypic shifts under chronic clenbuterol treatment, with AMPK and CamK2 probably playing a minor role. Moreover, the calpastatin-induced inhibition of hypertrophy under clenbuterol treatment was not related to a decreased mTOR-dependent initiation of protein translation

Assessment of Peak Inspiratory Flow in Young Infants with Acute Viral Bronchiolitis: Physiological Basis for Initial Flow Setting in Patients Supported with High-Flow Nasal Cannula

International audienc

Efficiency of physiotherapy with Caycedian Sophrology on children with asthma: A randomized controlled trial

International audienceBackground: Asthma is the most common chronic disease in pediatrics. Along with the usual drug therapy using corticosteroids and bronchodilators, some interest has been shown for adjuvant therapies, such as sophrology. However, the level of evidence for non‐pharmaceutical therapies in asthma remains low, especially in children. This study aimed to assess whether in children with asthma, peak expiratory flow (PEF) improved more after a sophrology session alongside standard treatment than after standard treatment alone.Methods: We carried out a prospective randomized controlled clinical trial among 74 children aged 6‐17 years old, hospitalized for an asthma attack. Group 1: conventional treatment (oxygen, corticosteroids, bronchodilators, physiotherapy) added to one session of sophrology. Group 2: conventional treatment alone. The primary outcome was the PEF variation between the initial and final evaluations (PEF2‐PEF1).Results: Demographic and clinical characteristics were similar in both groups at baseline. Measures before and after the sophrology session showed that the PEF increased by mean 30 L/min in the sophrology group versus 20 L/min in the control group (P = 0.02). Oxygen saturation increased by 1% versus 0% (P = 0.02) and the dyspnea score with visual analogue scale improved by two points point (P = 0.01). No differences were observed between the two groups in terms of duration of hospitalization, use and doses of conventional medical treatment (oxygen, corticosteroids, and bronchodilators), and quality of life scores.Conclusions: Sophrology appears as a promising adjuvant therapy to current guideline‐based treatment for asthma in children

Oxidative stress is decreased in physically active sickle cell SAD mice

International audienc