TFAM overexpression diminishes skeletal muscle atrophy after hindlimb suspension in mice.
TFAM overexpression diminishes skeletal muscle atrophy after hindlimb suspension in mice.
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TFAM 过表达可减少小鼠后肢悬吊后的骨骼肌萎缩。
DOI：
10.1016/j.abb.2018.12.015
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发表时间：
2019
影响因子：
3.9
通讯作者：
Tyagi,SureshC
中科院分区：
文献类型：
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作者：
Theilen,NicholasT;Jeremic,Nevena;Weber,GregoryJ;Tyagi,SureshC
本研究的目的是调查是否过表达线粒体转录因子A（TFAM）基因在转基因小鼠模型减少比目鱼肌和腓肠肌萎缩发生在后肢悬吊（HLS）。此外，我们的目的是观察在HLS之前在TFAM转基因小鼠中结合运动训练是否在预防骨骼肌萎缩方面具有协同作用。将过表达TFAM的雄性C57 BL/6 J转基因小鼠（12-14周龄）分配到对照组（T-对照）、7天HLS组（T-HLS）和7天HLS前2周运动训练组（T-Ex + HLS）。将这些组与分配至对照、7天HLS（HLS）、7天HLS之前的2周运动训练（Ex + HLS）和2周运动训练（Ex）的雄性C57 BL/6 J野生型（WT）小鼠（12-14周龄）进行比较。与野生型小鼠相比，过表达TFAM导致仅HLS后比目鱼肌重量与体重比降低8.3%和腓肠肌重量与体重比降低2.6%，野生型小鼠在HLS后比目鱼肌损失27.1%和腓肠肌损失21.5%。我们的数据表明TFAM可能在保护骨骼肌免于废用性萎缩中起关键作用，并且与抗氧化剂（SOD-2）的表达增加和潜在的氧化还原平衡相关。TFAM可能是一个有吸引力的分子的利益，潜在的，未来的治疗development.New和notworthyTo最好的我们的知识，这是第一次TFAM过表达转基因小鼠模型被用于废用诱导的骨骼肌萎缩的分析。在这里，我们提供了TFAM在减少骨骼肌萎缩中的潜在作用的证据。
The present study aims to investigate if overexpressing the mitochondrial transcription factor A (TFAM) gene in a transgenic mouse model diminishes soleus and gastrocnemius atrophy occurring during hindlimb suspension (HLS). Additionally, we aim to observe if combining exercise training in TFAM transgenic mice prior to HLS has a synergistic effect in preventing skeletal muscle atrophy. Male C57BL/6J-based transgenic mice (12–14 weeks old) overexpressing TFAM were assigned to a control (T-Control), 7-day HLS (T-HLS), and 2-week exercise training prior to 7-day HLS (T-Ex + HLS) groups. These groups were compared to male C57BL/6J wild-type (WT) mice (12–14 weeks old) assigned to Control, 7-day HLS (HLS), 2-week exercise training prior to 7-day HLS (Ex + HLS), and 2-week exercise training (Ex). Overexpressing TFAM results in a decrease of 8.3% in soleus and 2.6% in gastrocnemius muscle weight to bodyweight ratio after only HLS compared to wild-type mice incurring a loss of 27.1% in soleus and 21.5% in gastrocnemius muscle after HLS. Our data indicates TFAM may play a critical role in protecting skeletal muscle from disuse atrophy and is correlated with increased expression of antioxidants (SOD-2) and potential redox balance. TFAM may be an attractive molecule of interest for potential, future therapeutic development.New and noteworthyTo the best of our knowledge, this is the first time a TFAM overexpression transgenic mouse model is being used in the analysis of disuse-induced skeletal muscle atrophy. Here we provide evidence of a potential role for TFAM in diminishing skeletal muscle atrophy.