二甲双胍可增加营养不良性骨骼肌中过氧化物酶体增殖物激活受体γ共激活因子-1α和肌萎缩蛋白a的表达。
Metformin increases peroxisome proliferator-activated receptor γ Co-activator-1α and utrophin a expression in dystrophic skeletal muscle.
作者信息
Ljubicic Vladimir, Jasmin Bernard J
机构信息
Department of Cellular and Molecular Medicine, Faculty of Medicine, and Centre for Neuromuscular Disease, University of Ottawa, Ottawa, Ontario, K1H 8M5, Canada.
出版信息
Muscle Nerve. 2015 Jul;52(1):139-42. doi: 10.1002/mus.24692. Epub 2015 May 14.
INTRODUCTION
Metformin (MET) stimulates skeletal muscle AMP-activated protein kinase (AMPK), a key phenotype remodeling protein with emerging therapeutic relevance for Duchenne muscular dystrophy (DMD). Our aim was to identify the mechanism of impact of MET on dystrophic muscle.
METHODS
We investigated the effects of MET in cultured C2 C12 muscle cells and mdx mouse skeletal muscle. Expression of potent phenotypic modifiers was assessed, including peroxisome proliferator-activated receptor (PPAR)γ coactivator-1α (PGC-1α), PPARδ, and receptor-interacting protein 140 (RIP140), as well as that of the dystrophin-homolog, utrophin A.
RESULTS
In C2 C12 cells, MET augmented expression of PGC-1α, PPARδ, and utrophin A, whereas RIP140 content was reciprocally downregulated. MET treatment of mdx mice increased PGC-1α and utrophin A and normalized RIP140 levels.
CONCLUSIONS
In this study we identify the impact of MET on skeletal muscle and underscore the timeliness and importance of investigating MET and other AMPK activators as relevant therapeutics for DMD.
引言
二甲双胍（MET）可刺激骨骼肌中的AMP激活蛋白激酶（AMPK），这是一种关键的表型重塑蛋白，对杜氏肌营养不良症（DMD）具有新出现的治疗意义。我们的目的是确定MET对营养不良肌肉的影响机制。
方法
我们研究了MET对培养的C2 C12肌肉细胞和mdx小鼠骨骼肌的影响。评估了强效表型修饰剂的表达，包括过氧化物酶体增殖物激活受体（PPAR）γ共激活因子-1α（PGC-1α）、PPARδ和受体相互作用蛋白140（RIP140），以及肌营养不良蛋白同源物抗肌萎缩蛋白A的表达。
结果
在C2 C12细胞中，MET增强了PGC-1α、PPARδ和抗肌萎缩蛋白A的表达，而RIP140的含量则相应下调。用MET治疗mdx小鼠可增加PGC-1α和抗肌萎缩蛋白A的表达，并使RIP140水平恢复正常。
结论
在本研究中，我们确定了MET对骨骼肌的影响，并强调了研究MET和其他AMPK激活剂作为DMD相关治疗方法的及时性和重要性。
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