Analysis of altered gene expression in rat soleus muscle atrophied by disuse

Authors

  • Nathalie Cros,

    1. INSERM Unit 300, Faculté de Pharmacie, 15 avenue Charles Flahault, 34060, Montpellier cedex 01, France
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  • Andrei V. Tkatchenko,

    1. INSERM Unit 300, Faculté de Pharmacie, 15 avenue Charles Flahault, 34060, Montpellier cedex 01, France
    Current affiliation:
    1. Medical University of South Carolina, Department of Medicine, 600 MUSC complex, Suite 912, Charleston, SC 29425, USA.
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  • Didier F. Pisani,

    1. INSERM Unit 300, Faculté de Pharmacie, 15 avenue Charles Flahault, 34060, Montpellier cedex 01, France
    Current affiliation:
    1. CNRS UMR 6548, Faculté des Sciences, Parc Valrose, 06108 Nice cedex 2, France.
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  • Lilian Leclerc,

    1. INSERM Unit 300, Faculté de Pharmacie, 15 avenue Charles Flahault, 34060, Montpellier cedex 01, France
    Current affiliation:
    1. CNRS UMR 6548, Faculté des Sciences, Parc Valrose, 06108 Nice cedex 2, France.
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  • Jean J. Léger,

    1. INSERM Unit 300, Faculté de Pharmacie, 15 avenue Charles Flahault, 34060, Montpellier cedex 01, France
    Current affiliation:
    1. UFR Médecine, INSERM CJF 96-01, 1 rue Gaston Veil, BP 53508, 44035 Nantes cedex 1, France.
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  • Jean-François Marini,

    1. INSERM Unit 300, Faculté de Pharmacie, 15 avenue Charles Flahault, 34060, Montpellier cedex 01, France
    Current affiliation:
    1. CNRS UMR 6548, Faculté des Sciences, Parc Valrose, 06108 Nice cedex 2, France.
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  • Claude A. Dechesne

    Corresponding author
    1. INSERM Unit 300, Faculté de Pharmacie, 15 avenue Charles Flahault, 34060, Montpellier cedex 01, France
    Current affiliation:
    1. CNRS UMR 6548, Faculté des Sciences, Parc Valrose, 06108 Nice cedex 2, France.
    • CNRS UMR 6548, Faculté des Sciences, Parc Valrose, 06108 Nice cedex 2, France.
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Abstract

The present study involved a global analysis of genes whose expression was modified in rat soleus muscle atrophied after hindlimb suspension (HS). HS muscle unloading is a common model for muscle disuse that especially affects antigravity slow-twitch muscles such as the soleus muscle. A cDNA cloning strategy, based on suppression subtractive hybridization technology, led to the construction of two normalized soleus muscle cDNA libraries that were subtracted in opposite directions, i.e., atrophied soleus muscle cDNAs subtracted by control cDNAs and vice versa. Differential screening of the two libraries revealed 34 genes with altered expression in HS soleus muscle, including 11 novel cDNAs, in addition to the 2X and 2B myosin heavy chain genes expressed only in soleus muscles after HS. Gene up- and down-regulations were quantified by reverse Northern blot and classical Northern blot analysis. The 25 genes with known functions fell into seven important functional categories. The homogeneity of gene alterations within each category gave several clues for unraveling the interplay of cellular events implied in the muscle atrophy phenotype. In particular, our results indicate that modulations in slow- and fast-twitch-muscle component balance, the protein synthesis/secretion pathway, and the extracellular matrix/cytoskeleton axis are likely to be key molecular mechanisms of muscle atrophy. In addition, the cloning of novel cDNAs underlined the efficiency of the chosen technical approach and gave novel possibilities to further decipher the molecular mechanisms of muscle atrophy. J. Cell. Biochem. 83: 508–519, 2001. © 2001 Wiley-Liss, Inc.

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