Telomere shortening is associated to TRF1 and PARP1 overexpression in Duchenne muscular dystrophy

Aguennouz, M’Hammed; Vita, Gian Luca; Messina, Sonia; Cama, Annamaria; Lanzano, Natalia; Ciranni, Annamaria; Rodolico, Carmelo; Di Giorgio, Rosa Maria; Vita, Giuseppe

doi:10.1016/j.neurobiolaging.2010.01.008

« Previous Next »Neurobiology of Aging
Volume 32, Issue 12 , Pages 2190-2197, December 2011

Telomere shortening is associated to TRF1 and PARP1 overexpression in Duchenne muscular dystrophy

M’Hammed Aguennouz
- Department of Neurosciences, Psychiatry and Anaesthesiology, University of Messina, AOU Policlinico, Messina 98125, Italy
- Both authors equally contributed to this study.
Gian Luca Vita
- Department of Neurosciences, Psychiatry and Anaesthesiology, University of Messina, AOU Policlinico, Messina 98125, Italy
- Both authors equally contributed to this study.
Sonia Messina
- Department of Neurosciences, Psychiatry and Anaesthesiology, University of Messina, AOU Policlinico, Messina 98125, Italy
Annamaria Cama
- Department of Neurosciences, Psychiatry and Anaesthesiology, University of Messina, AOU Policlinico, Messina 98125, Italy
Natalia Lanzano
- Department of Neurosciences, Psychiatry and Anaesthesiology, University of Messina, AOU Policlinico, Messina 98125, Italy
Annamaria Ciranni
- Department of Neurosciences, Psychiatry and Anaesthesiology, University of Messina, AOU Policlinico, Messina 98125, Italy
Carmelo Rodolico
- Department of Neurosciences, Psychiatry and Anaesthesiology, University of Messina, AOU Policlinico, Messina 98125, Italy
Rosa Maria Di Giorgio
- Department of Biochemical, Physiological and Nutritional Sciences, University of Messina, AOU Policlinico, Messina 98125, Italy
Giuseppe Vita
- Department of Neurosciences, Psychiatry and Anaesthesiology, University of Messina, AOU Policlinico, Messina 98125, Italy
- Corresponding author. Unit of Neurology and Neuromuscular Diseases, AOU Policlinico, Via Consolare Valeria 1, 98125 Messina, Italy. Tel.: +39 090 2212793; fax: +39 090 2212789.

Received 23 July 2009; received in revised form 30 October 2009; accepted 14 January 2010. published online 08 February 2010.

Abstract

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.

Keywords: Telomere shortening, TRF1, PARP1, Duchenne muscular dystrophy, Replicative senescence