Regulation of ubiquitin-proteasome system, caspase enzyme activities, and extracellular proteinases in rat soleus muscle in response to unloading.
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.
Berthon
P
P
Laboratoire de Physiologie et de Biomécanique de l'Exercice Musculaire, Université Rennes 2, Rennes F-35000, France.
Duguez
S
S
Favier
F B
FB
Amirouche
A
A
Feasson
L
L
Vico
L
L
Denis
C
C
Freyssenet
D
D
D000818:Animals; D020169:Caspases / Q000378:metabolism*; D004268:DNA-Binding Proteins / Q000378:metabolism; D005786:Gene Expression Regulation; D018840:HSP70 Heat-Shock Proteins / Q000378:metabolism; D019417:Hindlimb Suspension / Q000502:physiology; D008297:Male; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D008928:Mitochondria / Q000378:metabolism; D018482:Muscle, Skeletal / Q000502:physiology*; D010447:Peptide Hydrolases / Q000378:metabolism*; D010641:Phenotype; D046988:Proteasome Endopeptidase Complex / Q000378:metabolism / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D014157:Transcription Factors / Q000378:metabolism; D025801:Ubiquitin / Q000502:physiology*; D014568:Urokinase-Type Plasminogen Activator / Q000378:metabolism
C091732:BCL2-associated athanogene 1 protein; D004268:DNA-Binding Proteins; D018840:HSP70 Heat-Shock Proteins; D014157:Transcription Factors; D025801:Ubiquitin; D010447:Peptide Hydrolases; D014568:Urokinase-Type Plasminogen Activator; D020169:Caspases; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9; D046988:Proteasome Endopeptidase Complex