Nemo Sud Clinical Centre for Neuromuscular Disorders, Messina University Hospital, Via Consolare Valeria 1, 98125, Messina, Italy.
Department of Clinical and Experimental Medicine, University of Messina, Via Consolare Valeria 1, 98125, Messina, Italy.
Mol Cell Biochem. 2020 Jul;470(1-2):189-197. doi: 10.1007/s11010-020-03761-3. Epub 2020 May 23.
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.
在杜氏肌营养不良症（DMD）中，端粒缩短被认为导致再生活动失败，从而促使卫星细胞过早衰老。本研究的目的是研究 DMD 小鼠模型（mdx 小鼠）的腓肠肌、比目鱼肌和膈肌中的端粒长度以及端粒重复结合因子 1（TRF1）、多聚（ADP-核糖）聚合酶 1（PARP1）和小鼠端粒酶逆转录酶（MTERT）的表达情况，以及慢性强制运动方案是否对其产生影响。我们的研究结果证实 mdx 肌肉中的端粒缩短，在膈肌中更为明显，其中运动引起的缩短比野生型小鼠更为明显。此外，我们首次在 mdx 中观察到 TRF1 和 PARP1 表达增加以及 MTERT 活性增强，运动进一步增强了这种作用。这些结果进一步支持了这样一种假说，即涉及端粒长度的机制失调，并可能为测试针对调节端粒维持的蛋白质的化合物开辟道路，作为治疗肌营养不良症的新策略。
