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Introduction Calpains are [Ca.sub.2+]-dependent cysteine proteases that constitute a large and diverse family. Skeletal muscle fibers contain ubiquitous calpain 1 and 2 but also calpain 3 (p94), which has recently [...], Calpains are [Ca.sub.2+] cysteine proteases that have been proposed to be involved in the cytoskeletal remodeling and wasting of skeletal muscle. Cumulative evidence also suggests that [β.sub.2]-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. Key words: β-agonist, clenbuterol, hypertrophy, muscle, phenotypical shift, rat, calpain activity, calpain autolysis. Les calpaines sont des proteases a cysteine dependantes du [Ca.sub.2+] qui pourraient etre impliquees dans le remodelage du cytosquelette et l'atrophie du muscle squelettique. Des etudes ont aussi suggere que les agonistes [β.sub.2] pourraient provoquer l'hypertrophie du muscle squelettique par un mecanisme qui semble lie a une enzyme proteolytique deependante du calcium. La presente etude a eu pour but d'examiner l'activite des calpaines dans les muscles de phenotype lent et rapide lors d'un traitement au clenbuterol chez le rat. Nous avons suivi, pendant 21 jours, revolution de l'activite des calpaines et de l'autolyse des calpaines ubiquistes 1 et 2, ainsi que le remodelage dans le muscle extenseur commun des orteils (ECO) et le muscle soleaire chez des rats Wistar males traites quotidiennement au clenbuterol (4 mg x [kg.sup.-1]). Apres 9 jours de traitement, nous avons observei une conversion des fibres lentes vers les rapides dans les 2 types de muscles, et note une hypertrophie dans l'ECO uniquement. Le muscle soleaire a monto une phase precoce d'apoptoneicrose, mise en evidence par une coloration a l'hematoxyline-eosine. L'activite calpalne totale a augmente dans les muscles ECO et soleaire des rats traites au clenbuterol. De plus, l'autolyse de la calpaine 1 a augmente significativement dans l'ECO apres 14 jours, ce qui n'a pas ete le cas dans le soleaire. L'autolyse de la calpaine 2 a augmente de maniere significative dans les 2 muscles 6 h apres la premiere injection de clenbuterol, ce qui indique que l'autolyse de la calpaine 2 induite par le clenbuterol se produit avant celle de la calpaine 1. Ces resultats laissent croire a une implication preferentielle de l'autolyse de la calpaine 2 par rapport a celle de la calpaine 1 dans les mecanismes sous-jacents au remodelage du muscle squelettique induit par le clenbuterol. Mots-cles: β-agoniste, clenbuterol, hypertrophie, muscle, conversion phenotypique, rat, activitee des calpaines, autolyse des calpaines. [Traduit par la Redaction]

CLENBUTEROL, a [beta]-agonist drug with affinity for [[beta].sub.1] and [[beta].sub.2] receptors, is licensed as a bronchodilator for use in human medicine in Spain and other countries in the European Community […]