Article (Scientific journals)
Functional muscle impairment in facioscapulohumeral muscular dystrophy is correlated with oxidative stress and mitochondrial dysfunction.
Turki, Ahmed; Hayot, Maurice; Carnac, Gilles et al.
2012In Free Radical Biology and Medicine, 53 (5), p. 1068-79
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Abstract :
[en] Facioscapulohumeral muscular dystrophy (FSHD), the most frequent muscular dystrophy, is an autosomal dominant disease. In most individuals with FSHD, symptoms are restricted to muscles of the face, arms, legs, and trunk. FSHD is genetically linked to contractions of the D4Z4 repeat array causing activation of several genes. One of these maps in the repeat itself and expresses the DUX4 (the double homeobox 4) transcription factor causing a gene deregulation cascade. In addition, analyses of the RNA or protein expression profiles in muscle have indicated deregulations in the oxidative stress response. Since oxidative stress affects peripheral muscle function, we investigated mitochondrial function and oxidative stress in skeletal muscle biopsies and blood samples from patients with FSHD and age-matched healthy controls, and evaluated their association with physical performances. We show that specifically, oxidative stress (lipid peroxidation and protein carbonylation), oxidative damage (lipofuscin accumulation), and antioxidant enzymes (catalase, copper-zinc-dependent superoxide dismutase, and glutathione reductase) were higher in FSHD than in control muscles. FSHD muscles also presented abnormal mitochondrial function (decreased cytochrome c oxidase activity and reduced ATP synthesis). In addition, the ratio between reduced (GSH) and oxidized glutathione (GSSG) was strongly decreased in all FSHD blood samples as a consequence of GSSG accumulation. Patients with FSHD also had reduced systemic antioxidative response molecules, such as low levels of zinc (a SOD cofactor), selenium (a GPx cofactor involved in the elimination of lipid peroxides), and vitamin C. Half of them had a low ratio of gamma/alpha tocopherol and higher ferritin concentrations. Both systemic oxidative stress and mitochondrial dysfunction were correlated with functional muscle impairment. Mitochondrial ATP production was significantly correlated with both quadriceps endurance (T(LimQ)) and maximal voluntary contraction (MVC(Q)) values (rho=0.79, P=0.003; rho=0.62, P=0.05, respectively). The plasma concentration of oxidized glutathione was negatively correlated with the T(LimQ), MVC(Q) values, and the 2-min walk distance (MWT) values (rho=-0.60, P=0.03; rho=-0.56, P=0.04; rho=-0.93, P<0.0001, respectively). Our data characterized oxidative stress in patients with FSHD and demonstrated a correlation with their peripheral skeletal muscle dysfunction. They suggest that antioxidants that might modulate or delay oxidative insult may be useful in maintaining FSHD muscle functions.
Disciplines :
Surgery
Author, co-author :
Turki, Ahmed
Hayot, Maurice
Carnac, Gilles
Pillard, Fabien
Passerieux, Emilie
Bommart, Sebastien
Raynaud de Mauverger, Eric
Hugon, Gerald
PINCEMAIL, Joël ;  Centre Hospitalier Universitaire de Liège - CHU > Chirurgie cardio-vasculaire
Pietri, Sylvia
Lambert, Karen
Belayew, Alexandra
Vassetzky, Yegor
Juntas Morales, Raul
Mercier, Jacques
Laoudj-Chenivesse, Dalila
More authors (6 more) Less
Language :
English
Title :
Functional muscle impairment in facioscapulohumeral muscular dystrophy is correlated with oxidative stress and mitochondrial dysfunction.
Publication date :
2012
Journal title :
Free Radical Biology and Medicine
ISSN :
0891-5849
eISSN :
1873-4596
Publisher :
Elsevier, Amsterdam, Netherlands
Volume :
53
Issue :
5
Pages :
1068-79
Peer reviewed :
Peer Reviewed verified by ORBi
Commentary :
Copyright (c) 2012 Elsevier Inc. All rights reserved.
Available on ORBi :
since 14 December 2012

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