Handschin Christoph, Kobayashi Yvonne M, Chin Sherry, Seale Patrick, Campbell Kevin P, Spiegelman Bruce M
Dana-Farber Cancer Institute and Department of Cell Biology, Harvard Medical School, Boston, Massachusetts 02115, USA.
Genes Dev. 2007 Apr 1;21(7):770-83. doi: 10.1101/gad.1525107.
The coactivator PGC-1alpha mediates key responses of skeletal muscle to motor nerve activity. We show here that neuregulin-stimulated phosphorylation of PGC-1alpha and GA-binding protein (GABP) allows recruitment of PGC-1alpha to the GABP complex and enhances transcription of a broad neuromuscular junction gene program. Since a subset of genes controlled by PGC-1alpha and GABP is dysregulated in Duchenne muscular dystrophy (DMD), we examined the effects of transgenic PGC-1alpha 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-1alpha levels in skeletal muscle could represent a novel avenue to prevent or treat DMD.
辅激活因子 PGC-1α 介导骨骼肌对运动神经活动的关键反应。我们在此表明，神经调节蛋白刺激的 PGC-1α 和 GA 结合蛋白（GABP）磷酸化可使 PGC-1α 募集至 GABP 复合物，并增强广泛的神经肌肉接头基因程序的转录。由于在杜兴氏肌营养不良症（DMD）中，受 PGC-1α 和 GABP 调控的一部分基因表达失调，我们研究了转基因 PGC-1α 对 mdx 小鼠肌肉的影响。这些动物在 DMD 特征参数方面有所改善，包括肌肉组织学、跑步能力和血浆肌酸激酶水平。因此，控制骨骼肌中 PGC-1α 的水平可能是预防或治疗 DMD 的新途径。
