Telomere shortening is associated to TRF1 and PARP1 overexpression in Duchenne muscular dystrophy.
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.
Aguennouz
M'Hammed
M
Department of Neurosciences, Psychiatry and Anaesthesiology, University of Messina, AOU Policlinico, Messina 98125, Italy.
Vita
Gian Luca
GL
Messina
Sonia
S
Cama
Annamaria
A
Lanzano
Natalia
N
Ciranni
Annamaria
A
Rodolico
Carmelo
C
Di Giorgio
Rosa Maria
RM
Vita
Giuseppe
G
D002648:Child; D002675:Child, Preschool; D005786:Gene Expression Regulation; D006801:Humans; D007223:Infant; D020388:Muscular Dystrophy, Duchenne / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D000071137:Poly (ADP-Ribose) Polymerase-1; D011065:Poly(ADP-ribose) Polymerases / Q000096:biosynthesis* / Q000235:genetics; D052097:Quadriceps Muscle / Q000473:pathology; D059506:Telomere Shortening / Q000235:genetics*; D035321:Telomeric Repeat Binding Protein 1 / Q000096:biosynthesis* / Q000235:genetics
D035321:Telomeric Repeat Binding Protein 1; C499320:PARP1 protein, human; D000071137:Poly (ADP-Ribose) Polymerase-1; D011065:Poly(ADP-ribose) Polymerases