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TFAM overexpression diminishes skeletal muscle atrophy after hindlimb suspension in mice

Author:
Theilen, Nicholas T., Jeremic, Nevena, Weber, Gregory J., Tyagi, Suresh C.
Source:
Archives of biochemistry and biophysics 2019 v.666 pp. 138-147
ISSN:
0003-9861
Subject:
animal models, antioxidants, body weight, exercise, gene overexpression, genes, males, mice, mitochondria, muscles, muscular atrophy, skeletal muscle, superoxide dismutase, therapeutics, transcription factors, transgenic animals
Abstract:
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.To 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.
Agid:
6257366