Casted-immobilization downregulates glucocorticoid receptor expression in rat slow-twitch soleus muscle

Shogo Sato, Hideki Suzuki, Hisaya Tsujimoto, Ken Shirato, Kaoru Tachiyashiki, Kazuhiko Imaizumi

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    11 Citations (Scopus)

    Abstract

    Aims: Glucocorticoids bindtothe glucocorticoid receptor (GR) and increase catabolismof muscle proteins via the ubiquitin-proteasome pathway. Activation of β 2-adrenergic receptor (β 2-AR) in skeletal muscle has been shown to induce muscle hypertrophy by promoting muscle protein synthesis and/or attenuating protein degradation. The aim of this study was to investigate the correlation between disuse-induced muscle atrophy, and expression of GR and β 2-AR. Methods: Rats were subjected to casted-immobilization (knee and foot arthrodesis), a model for muscle disuse, for 10 days. Fast-twitch (extensor digitorum longus: EDL) and slow-twitch (soleus: SOL) muscles were isolated and subsequently used for analysis. The expression of GR and β 2-AR was analyzed by real-time RT-PCR and western blotting. In addition, we analyzed plasma catecholamine and corticosterone concentrations by ELISA. Key findings: Casted-immobilization- induced muscle atrophy was much greater in the SOL muscle than in the EDL muscle. Casted-immobilization decreased the expression of GR mRNA and protein in the SOL muscle but not in the EDL muscle. Although the expression of β 2-AR protein in the cytosol and membrane-rich fractions was not changed by casted-immobilization in either muscle, casted-immobilization decreased the expression of β 2-AR mRNA in the SOL muscle. Plasma catecholamine and corticosterone concentrations, however, were largely unaffected by casted-immobilization during the experimental period. Significance: This study provides evidence that casted-immobilization-induced muscle disuse downregulates GR expression in slow-twitch muscle. These results suggest that muscle disuse suppresses glucocorticoid signals, such as muscle protein breakdown and transcription of the β 2-AR gene, via downregulation of GR expression in slow-twitch muscle.

    Original languageEnglish
    Pages (from-to)962-967
    Number of pages6
    JournalLife Sciences
    Volume89
    Issue number25-26
    DOIs
    Publication statusPublished - 2011 Dec 19

    Keywords

    • Glucocorticoid receptor β - adrenergic receptor
    • Immobilization
    • Muscle atrophy

    ASJC Scopus subject areas

    • Pharmacology, Toxicology and Pharmaceutics(all)
    • Biochemistry, Genetics and Molecular Biology(all)

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  • Cite this

    Sato, S., Suzuki, H., Tsujimoto, H., Shirato, K., Tachiyashiki, K., & Imaizumi, K. (2011). Casted-immobilization downregulates glucocorticoid receptor expression in rat slow-twitch soleus muscle. Life Sciences, 89(25-26), 962-967. https://doi.org/10.1016/j.lfs.2011.10.008