Coordinate activation of lysosomal, Ca2+-activated and ATP-ubiquitin-dependent proteinases in the unweighted rat soleus muscle

Biochemical Journal - Tập 316 Số 1 - Trang 65-72 - 1996
Daniel Taillandier1, E Aurousseau1, Dominique MEYNIAL-DENIS1, Daniel Béchet2, André Ducastaing3, Xavier Bigard4, C. Y. Guezennec4, Hans-Peter SCHMID5, Didier Attaix1
1Centre de Recherche en Nutrition Humaine and Institut National de la Recherche Agronomique, Unité d'Étude du Métabolisme Azoté, France
2Unité de Nutrition Cellulaire et Moléculaire, 63122 Ceyrat, France
3ISTAB and Université de Bordeaux I, 33405 Talence, France
4Centre d'Études et de Recherches de Médecine Aérospatiale, Laboratoire de Physiologie Métabolique, 91228 Brétigny-sur-Orge, France
5Université Blaise Pascal, Clermont-Ferrand II, Biochimie, 63177 Aubière Cédex, France

Tóm tắt

Nine days of hindlimb suspension resulted in atrophy (55%) and loss of protein (53%) in rat soleus muscle due to a marked elevation in protein breakdown (66%, P < 0.005). To define which proteolytic system(s) contributed to this increase, soleus muscles from unweighted rats were incubated in the presence of proteolytic inhibitors. An increase in lysosomal and Ca2+-activated proteolysis (254%, P < 0.05) occurred in the atrophying incubated muscles. In agreement with the measurements in vitro, cathepsin B, cathepsins B+L and m-calpain enzyme activities increased by 111%, 92% and 180% (P < 0.005) respectively in the atrophying muscles. Enhanced mRNA levels for these proteinases (P < 0.05 to P < 0.001) paralleled the increased enzyme activities, suggesting a transcriptional regulation of these enzymes. However, the lysosomal and Ca2+-dependent proteolytic pathways accounted for a minor part of total proteolysis in both control (9%) and unweighted rats (18%). Furthermore the inhibition of these pathways failed to suppress increased protein breakdown in unweighted muscle. Thus a non-lysosomal Ca2+-independent proteolytic process essentially accounted for the increased proteolysis and subsequent muscle wasting. Increased mRNA levels for ubiquitin, the 14 kDa ubiquitin-conjugating enzyme E2 (involved in the ubiquitylation of protein substrates) and the C2 and C9 subunits of the 20 S proteasome (i.e. the proteolytic core of the 26 S proteasome that degrades ubiquitin conjugates) were observed in the atrophying muscles (P < 0.02 to P < 0.001). Analysis of C9 mRNA in polyribosomes showed equal distribution into both translationally active and inactive mRNA pools, in either unweighted or control rats. These results suggest that increased ATP-ubiquitin-dependent proteolysis is most probably responsible for muscle wasting in the unweighted soleus muscle.

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Biochemical Journal

Tập 316 Số 1

65-72

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