Abstract
In Duchenne muscular dystrophy (DMD), telomere shortening has been postulated to contribute to the failure of regenerative activity promoting the premature senescence of satellite cells. The aim of the present study was to investigate the telomere length and the expression of telomeric repeat-binding factor-1 (TRF1), poly (ADP-ribose) polymerase-1 (PARP1) and mouse telomerase reverse transcriptase (MTERT) in gastrocnemius, tibialis anterior and diaphragm muscles of the murine model of DMD, the mdx mouse and whether a chronic protocol of forced exercise impacts on them. Our results confirmed a telomere shortening in mdx muscles, more evident in the diaphragm, in which exercise induced a greater shortening than in wild-type mice. Moreover, we showed for the first time in mdx an increased TRF1 and PARP1 expression and an augmented activity of MTERT, further enhanced by exercise. These results reinforce the hypothesis that a deregulation of mechanisms involved in telomere length occurs and may pave the way for the test of compounds targeting proteins modulating telomere maintenance as a novel strategy to treat dystrophinopathies.
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Funding
Part of the project has been supported by MIUR PRIN 2015 to ADL [n. 2015MJBEM2_005]. The funders had no role in study design, data collection and analysis, decision to publish or preparation of the manuscript.
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GLV, MA, GV, ADL and SM contributed to the conception and design of the study. MS, FS, PM, RO, FP, NL and SR performed the experiments and analysed the data. All authors contributed to manuscript draft. All authors approved the final version.
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Vita, G.L., Aguennouz, M., Sframeli, M. et al. Effect of exercise on telomere length and telomere proteins expression in mdx mice. Mol Cell Biochem 470, 189–197 (2020). https://doi.org/10.1007/s11010-020-03761-3
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DOI: https://doi.org/10.1007/s11010-020-03761-3