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Regulation of ubiquitin–proteasome system, caspase enzyme activities, and extracellular proteinases in rat soleus muscle in response to unloading

  • Skeletal Muscle
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Abstract

In the present study, we determined the impact of 5 and 10 days of muscle deconditioning induced by hindlimb suspension (HS) on the ubiquitin–proteasome system of protein degradation and caspase enzyme activities in rat soleus muscles. A second goal was to determine whether activities of matrix metalloproteinase-2/9 (MMP-2/9) and urokinase-type/tissue-type plasminogen activator (PAs) were responsive to HS. As expected, HS led to a pronounced atrophy of soleus muscle. Level of ubiquitinated proteins, chymotrypsin-like activity of 20S proteasome, and Bcl-2-associated gene product-1 protein level were all transitory increased in response to 5 days of HS. These changes may thus potentially account for the decrease in muscle mass observed in response to 5 days of HS. Caspase-3 activity was significantly increased throughout the experimental period, whereas activities of caspase-6, another effector caspase, and caspase-9, the mitochondrial-dependent activator of both caspase-3 and -6, were only increased in response to 10 days of HS. This suggests that caspase-3 may be regulated through mitochondrial-independent and mitochondrial-dependent mechanisms in response to HS. Finally, MMP-2/9 activities remained unchanged, whereas PAs activities were increased after 5 days of HS. Overall, these data suggest that time-dependent regulation of intracellular and extracellular proteinases are important in setting the new phenotype of rat soleus muscle in response to HS.

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Acknowledgements

The authors thank D. Desplanches for critical review of the manuscript. We are grateful to F. Sabot for his help with enzyme assays.

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Authors and Affiliations

  1. Laboratoire de Physiologie et de Biomécanique de l’Exercice Musculaire, Université Rennes 2, Rennes, F-35000, France

    P. Berthon

  2. Unité Physiologie et Physiopathologie de l’Exercice et Handicap, EA3062, Université Jean Monnet, Saint-Etienne, F-42000, France

    S. Duguez, F. B. Favier, A. Amirouche, L. Feasson, C. Denis & D. Freyssenet

  3. INSERM, U890, Saint-Etienne, France

    L. Vico

  4. IFR143, Faculté de Médecine, Université Jean Monnet, Saint-Etienne, France

    S. Duguez, F. B. Favier, A. Amirouche, L. Feasson, L. Vico, C. Denis & D. Freyssenet

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Berthon, P., Duguez, S., Favier, F.B. et al. Regulation of ubiquitin–proteasome system, caspase enzyme activities, and extracellular proteinases in rat soleus muscle in response to unloading. Pflugers Arch - Eur J Physiol 454, 625–633 (2007). https://doi.org/10.1007/s00424-007-0230-6

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  • DOI: https://doi.org/10.1007/s00424-007-0230-6

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