Myosin loss in denervated rat soleus muscle after dexamethasone treatment
Myosin loss in denervated rat soleus muscle after dexamethasone treatment
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DOI：
10.1159/000084113
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发表时间：
2005-01-01
期刊：
影响因子：
5
通讯作者：
Tsuda, T
中科院分区：
文献类型：
--
作者：
Horinouchi, H;Kumamoto, T;Tsuda, T
目的：危重病肌病（CIM）是一种急性肌病，出现在危重病或暴露于皮质类固醇和神经肌肉阻滞剂。其病理特征是粗肌球蛋白丝的选择性丢失。我们的目的是进一步了解这种肌病中肌球蛋白丢失的病理机制。研究方法：为了阐明肌球蛋白重链（MHC）和泛素连接酶atrogin-1在这种肌病的表达，组织学，免疫组化，SDS-PAGE和半定量逆转录聚合酶链反应研究进行神经支配和去神经支配大鼠比目鱼肌肌肉生理盐水和地塞米松治疗后。结果：地塞米松处理的大鼠失神经肌肉表现出明显的MHC丢失。泛素连接酶atrogin-1的mRNA表达在去神经地塞米松处理的肌肉中显著增加，表明泛素-蛋白酶体途径在CIM的肌肉萎缩中起重要作用。此外，MHC I，肌球蛋白亚型的mRNA水平下降，在去神经地塞米松治疗的肌肉。结论：我们的研究结果表明，肌球蛋白的转录速率改变，以及多种泛素连接酶的上调，可能是这种肌病中选择性肌球蛋白丢失的原因。版权所有（C）2005 S. Karger AG，巴塞尔。
Objective: Critical illness myopathy (CIM) is an acute myopathy that appears in the setting of critical illness or during exposure to corticosteroids and neuromuscular blocking agents. Its pathological feature is selective loss of thick myosin filaments. Our aim is to gain further insight into the pathomechanism of myosin loss in this myopathy. Methods: To clarify the expression of myosin heavy chain (MHC) and ubiquitin ligase atrogin-1 in this myopathy, histological, immunohistochemical, SDS-PAGE, and semiquantitative reverse transcriptase-polymerase chain reaction studies were performed on innervated and denervated rat soleus muscles after saline and dexamethasone treatments. Results: Denervated muscles from dexamethasone-treated rats showed marked MHC loss. The mRNA expression of ubiquitin ligase atrogin-1 was significantly increased in denervated dexamethasone-treated muscles, suggesting that the ubiquitin-proteasome pathway plays an important role in muscular wasting in CIM. Furthermore, mRNA levels of MHC I, a myosin isoform, were decreased in the denervated dexamethasone-treated muscles. Conclusion: Our findings suggest that an altered transcription rate of myosin, as well as the upregulation of multiple ubiquitin ligases, may be responsible for selective myosin loss in this myopathy. Copyright (C) 2005 S. Karger AG, Basel.