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The effect of ARC ablation on skeletal muscle morphology, function, and apoptotic signaling during aging

Item Type:Article
Title:The effect of ARC ablation on skeletal muscle morphology, function, and apoptotic signaling during aging
Creators Name:Vorobej, K. and Mitchell, A.S. and Smith, I.C. and Donath, S. and Tupling, A.R. and Quadrilatero, J.
Abstract:Augmented apoptotic signaling can result in degradation of skeletal muscle proteins and loss of myonuclei, ultimately contributing to muscle atrophy and contractile dysfunction. Apoptosis repressor with caspase recruitment domain (ARC) is an anti-apoptotic protein highly expressed in skeletal muscle. Here we examined the role of ARC on age-related skeletal muscle apoptosis and wasting by utilizing an ARC-deficient mouse model. Aged mice displayed a number of morphological, phenotypic, and contractile alterations in both soleus and plantaris muscle with aging. Although no differences were found in proteolytic enzyme activity, ARC protein decreased while several anti-apoptotic proteins (e.g., BCL2, BCLXL, HSP70, and XIAP) and the release of mitochondrial housed protein (i.e., SMAC, AIF) increased in aged muscle. Importantly, ARC KO mice had low muscle weights and fewer fibers in soleus, with 2-year-old ARC KO mice displaying lower mitochondrial BCL2 protein along with augmented release of CYTC and SMAC in red/oxidative muscle. Overall, these results indicate that aged skeletal muscle undergoes atrophy as well as contractile and fiber type composition alterations despite an increase in anti-apoptotic protein expression. Although some mitochondrial-specific apoptotic alterations occurred in skeletal muscle due to ARC ablation over the lifespan, our data suggest that ARC may not have a large influence during skeletal muscle aging.
Keywords:Aging, Apoptosis, Apoptosis Regulatory Proteins, Caspase Activation and Recruitment Domain, Caspases, Cellular Senescence, Muscle Proteins, Signal Transduction, Skeletal Muscle, Animals, Mice
Source:Experimental Gerontology
Page Range:69-79
Date:January 2018
Official Publication:https://doi.org/10.1016/j.exger.2017.10.018
PubMed:View item in PubMed

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