Casted-immobilization downregulates glucocorticoid receptor expression in rat slow-twitch soleus muscle
Casted-immobilization downregulates glucocorticoid receptor expression in rat slow-twitch soleus muscle
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DOI：
10.1016/j.lfs.2011.10.008
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发表时间：
2011-12-19
期刊：
影响因子：
6.1
通讯作者：
Imaizumi, Kazuhiko
中科院分区：
文献类型：
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作者：
Sato, Shogo;Suzuki, Hideki;Imaizumi, Kazuhiko
目的：糖皮质激素与糖皮质激素受体(GR)结合，通过泛素-蛋白酶体途径增加肌肉蛋白质的分解代谢。骨骼肌中β(2)-肾上腺素能受体(beta(2)-AR)的激活可通过促进肌肉蛋白质合成和/或抑制蛋白质降解而诱导肌肉肥大。本研究的目的是探讨废用性肌萎缩与GR和β(2)-AR表达的相关性。方法：采用石膏固定(膝关节和足部关节融合术)的肌肉废用模型，连续10天。分离快抽动肌(指长伸肌：EDL)和慢抽动肌(比目鱼肌：SOL)并用于分析。用实时定量RT-PCR和Western blotting分析GR和β(2)-AR的表达。此外，我们用ELISA分析了血浆儿茶酚胺和皮质酮的浓度。主要发现：铸型制动引起的肌肉萎缩在SOL肌肉中比在EDL肌肉中严重得多。铸型制动可降低SOL肌GR基因和蛋白的表达，但不影响EDL肌GR基因和蛋白的表达。虽然铸型固定化不改变β(2)-AR蛋白在胞浆和富膜组份中的表达，但铸型固定化降低了溶胶肌中β(2)-AR mRNA的表达。然而，在实验期间，石膏制动对血浆儿茶酚胺和皮质酮浓度基本没有影响。意义：本研究提供了石膏制动诱导的肌肉停用下调慢抽动肌肉GR表达的证据。这些结果表明，肌肉停用通过下调慢抽动肌肉中GR的表达来抑制糖皮质激素信号，如肌肉蛋白质分解和β(2)-AR基因的转录。(C)2011 Elsevier Inc.保留所有权利。
Aims: Glucocorticoids bind to the glucocorticoid receptor (GR) and increase catabolism of muscle proteins via the ubiquitin-proteasome pathway. Activation of beta(2)-adrenergic receptor (beta(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 beta(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 beta(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 beta(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 beta(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 beta(2)-AR gene, via downregulation of GR expression in slow-twitch muscle. (C) 2011 Elsevier Inc. All rights reserved.