Skeletal muscle fiber-type switching, exercise intolerance, and myopathy in PGC-1α muscle-specific knock-out animals
Skeletal muscle fiber-type switching, exercise intolerance, and myopathy in PGC-1α muscle-specific knock-out animals
复制标题
DOI：
10.1074/jbc.m704817200
复制
发表时间：
2007-10-12
影响因子：
4.8
通讯作者：
Spiegelman, Bruce M.
中科院分区：
文献类型：
--
作者：
Handschin, Christoph;Chin, Sherry;Spiegelman, Bruce M.
转录辅激活因子过氧化物酶体增殖物激活受体γ辅激活因子1 α（PGC-1 α）是骨骼肌神经肌肉活动的关键整合因子。PGC-1 α在肌肉中的异位表达导致线粒体数量和功能增加，以及氧化、抗疲劳肌纤维增加。全身PGC-1 α基因敲除小鼠具有非常复杂的表型，但不具有显著的骨骼肌表型。因此，我们分析了骨骼肌特异性PGC-1 α基因敲除小鼠，以确定PGC-1 α在骨骼肌功能中的特定作用。这些小鼠表现出从氧化I型和IIa型向IIx型和IIb型肌纤维的转变。此外，骨骼肌特异性PGC-1 α基因敲除动物在跑步机跑步后耐力降低，并表现出纤维损伤和炎症标志物升高。我们的数据表明PGC-1 α在维持正常纤维类型组成和运动后肌纤维完整性方面起关键作用。
The transcriptional coactivator peroxisome proliferator-activated receptor gamma coactivator 1 alpha (PGC-1 alpha) is a key integrator of neuromuscular activity in skeletal muscle. Ectopic expression of PGC-1 alpha in muscle results in increased mitochondrial number and function as well as an increase in oxidative, fatigue-resistant muscle fibers. Whole body PGC-1 alpha knock-out mice have a very complex phenotype but do not have a marked skeletal muscle phenotype. We thus analyzed skeletal muscle-specific PGC-1 alpha knock-out mice to identify a specific role for PGC-1 alpha in skeletal muscle function. These mice exhibit a shift from oxidative type I and IIa toward type IIx and IIb muscle fibers. Moreover, skeletal muscle-specific PGC-1 alpha knock-out animals have reduced endurance capacity and exhibit fiber damage and elevated markers of inflammation following treadmill running. Our data demonstrate a critical role for PGC-1 alpha in maintenance of normal fiber type composition and of muscle fiber integrity following exertion.