Department of Neurosciences, Psychiatry and Anaesthesiology, University of Messina, AOU Policlinico, Messina 98125, Italy.
Neurobiol Aging. 2011 Dec;32(12):2190-7. doi: 10.1016/j.neurobiolaging.2010.01.008. Epub 2010 Feb 5.
Telomere shortening is thought to contribute to premature senescence of satellite cells in Duchenne muscular dystrophy (DMD) muscle. Telomeric repeat binding factor-1 (TRF1) and poly (ADP-ribose) polymerase-1 (PARP1) are proteins known to modulate telomerase reverse transcriptase (TERT) activity, which controls telomere elongation. Here we show that an age-dependent telomere shortening occurs in DMD muscles and is associated to overexpression of mRNA and protein levels of TRF1 and PARP1. TERT expression and activity are detectable in normal control muscles and they slightly increase in DMD. This is the first demonstration of TRF1 and PARP1 overexpression in DMD muscles. They can be directly involved in replicative senescence of satellite cells and/or in the pathogenetic cascade through a cross-talk with oxidative stress and inflammatory response. Modulation of these events by TRF1 or PARP1 inhibition might represent a novel strategy for treatment of DMD and other muscular dystrophies.
端粒缩短被认为导致杜氏肌营养不良症（DMD）肌肉卫星细胞的过早衰老。端粒重复结合因子-1（TRF1）和聚（ADP-核糖）聚合酶-1（PARP1）是已知调节端粒酶逆转录酶（TERT）活性的蛋白质，端粒酶逆转录酶控制端粒的延长。在这里，我们表明端粒在 DMD 肌肉中随着年龄的增长而缩短，并且与 TRF1 和 PARP1 的 mRNA 和蛋白水平的过度表达相关。TERT 表达和活性在正常对照肌肉中可检测到，并且在 DMD 中略有增加。这是首次在 DMD 肌肉中证明 TRF1 和 PARP1 的过度表达。它们可以直接参与卫星细胞的复制性衰老，和/或通过与氧化应激和炎症反应的串扰参与致病级联。通过 TRF1 或 PARP1 抑制来调节这些事件可能代表治疗 DMD 和其他肌肉营养不良症的新策略。
