Electric pulse stimulation of cultured murine muscle cells reproduces gene expression changes of trained mouse muscle.

Electric pulse stimulation of cultured murine muscle cells reproduces gene expression changes of trained mouse muscle.
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DOI:
10.1371/journal.pone.0010970
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发表时间:
2010-06-04
期刊:
影响因子:
3.7
通讯作者:
Handschin C
Handschin C
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Burch N;Arnold AS;Item F;Summermatter S;Brochmann Santana Santos G;Christe M;Boutellier U;Toigo M;Handschin C

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充足的身体活动是健康生活方式的核心。然而,调节运动有益效果的分子机制仍然是个谜。这种知识差距是由于缺乏合适的实验模型系统造成的。因此,我们优化了肌肉细胞的电脉冲刺激,以密切重现在受过训练的骨骼肌中观察到的基因表达的可塑性变化。使用过氧化物酶体增殖物激活受体 γ 共激活剂 1α (PGC-1α) 作为耐力训练肌纤维的标记物建立了确切的实验条件。随后,我们将肌肉细胞系统中代谢和肌原纤维基因的相对表达的变化与在急性或重复的跑步机运动后在体内观察到的小鼠肌肉中观察到的变化进行了比较。重要的是,在电刺激的 C2C12 小鼠肌肉细胞中,定性转录适应几乎与受过训练的肌肉中的转录适应相同,但不同于运动对肌肉基因表达的急性影响。此外,肌原纤维蛋白表达的显着变化表明这种刺激可用于调节培养物中肌肉细胞的纤维类型。因此,我们的数据描述了一种实验细胞培养模型,用于研究骨骼肌适应身体活动的至少一些转录方面。该系统将有助于研究调节肌肉运动适应的分子机制。
Adequate levels of physical activity are at the center of a healthy lifestyle. However, the molecular mechanisms that mediate the beneficial effects of exercise remain enigmatic. This gap in knowledge is caused by the lack of an amenable experimental model system. Therefore, we optimized electric pulse stimulation of muscle cells to closely recapitulate the plastic changes in gene expression observed in a trained skeletal muscle. The exact experimental conditions were established using the peroxisome proliferator-activated receptor γ coactivator 1α (PGC-1α) as a marker for an endurance-trained muscle fiber. We subsequently compared the changes in the relative expression of metabolic and myofibrillar genes in the muscle cell system with those observed in mouse muscle in vivo following either an acute or repeated bouts of treadmill exercise. Importantly, in electrically stimulated C2C12 mouse muscle cells, the qualitative transcriptional adaptations were almost identical to those in trained muscle, but differ from the acute effects of exercise on muscle gene expression. In addition, significant alterations in the expression of myofibrillar proteins indicate that this stimulation could be used to modulate the fiber-type of muscle cells in culture. Our data thus describe an experimental cell culture model for the study of at least some of the transcriptional aspects of skeletal muscle adaptation to physical activity. This system will be useful for the study of the molecular mechanisms that regulate exercise adaptation in muscle.