PGC-1α regulates the neuromuscular junction program and ameliorates Duchenne muscular dystrophy
PGC-1α regulates the neuromuscular junction program and ameliorates Duchenne muscular dystrophy
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DOI：
10.1101/gad.1525107
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发表时间：
2007-04-01
影响因子：
10.5
通讯作者：
Spiegelman, Bruce M.
中科院分区：
文献类型：
--
作者：
Handschin, Christoph;Kobayashi, Yvonne M.;Spiegelman, Bruce M.
辅激活因子PGC-1 α介导骨骼肌对运动神经活动的关键反应。我们在这里表明，神经调节素刺激的PGC-1 α和GA结合蛋白（GABP）的磷酸化允许招聘PGC-1 α的GABP复合物，并增强了广泛的神经肌肉接头基因程序的转录。由于PGC-1 α和GABP控制的基因子集在杜氏肌营养不良症（DMD）中失调，我们研究了转基因PGC-1 α在mdx小鼠肌肉中的作用。这些动物表现出DMD特征参数的改善，包括肌肉组织学、跑步表现和血浆肌酸激酶水平。因此，控制骨骼肌中的PGC-1 α水平可能代表预防或治疗DMD的新途径。
The coactivator PGC-1 alpha mediates key responses of skeletal muscle to motor nerve activity. We show here that neuregulin-stimulated phosphorylation of PGC-1 alpha and GA-binding protein (GABP) allows recruitment of PGC-1 alpha to the GABP complex and enhances transcription of a broad neuromuscular junction gene program. Since a subset of genes controlled by PGC-1 alpha and GABP is dysregulated in Duchenne muscular dystrophy (DMD), we examined the effects of transgenic PGC-1 alpha in muscle of mdx mice. These animals show improvement in parameters characteristic of DMD, including muscle histology, running performance, and plasma creatine kinase levels. Thus, control of PGC-1 alpha levels in skeletal muscle could represent a novel avenue to prevent or treat DMD.