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Increased levels of adenine nucleotide translocator 1 protein and response to oxidative stress are early events in facioscapulohumeral muscular dystrophy muscle

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Abstract

Facioscapulohumeral muscular dystrophy (FSHD), an autosomal dominant neuromuscular disorder, has been causally related to deletion of tandemly arrayed 3.3 kb repeats (D4Z4) on chromosome 4q35. Although increased expression of several 4q35 genes has been reported, two recent studies dispute this, finding no significant changes in the transcriptional level of any of the 4q35 genes, among which is the heart and muscle-specific isoform of the adenine nucleotide translocator (ANT1). We found markedly increased levels of ANT1 protein in both unaffected and affected FSHD muscles in comparison to control healthy muscles. Comparative protein expression analysis between healthy, Duchenne muscular dystrophy, and FSHD muscle shows that proteins involved in mitochondrial function and protection from oxidative stress are also reproducibly and specifically modified in all FSHD muscles, including clinically unaffected muscles. Increased ANT1 expression and mitochondrial dysfunction may thus be initial events in FSHD pathogenesis and represent potential therapeutic targets.

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Abbreviations

2-DE :

Two-dimensional gel electrophoresis

ANT :

Adenine nucleotide translocator

DMD :

Duchenne muscular dystrophy

FSHD :

Facioscapulohumeral muscular dystrophy

MALDI-TOF :

Matrix-assisted laser desorption/ionization time-of-flight mass spectrometry

PAGE :

Polyacrylamide gel electrophoresis

pI :

Isoelectric point

ROS :

Reactive oxygen species

SDS :

Sodium dodecyl sulfate

SOD :

Cu/Zn superoxide dismutase

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Acknowledgements

We are grateful to the patients from the Association FSH Europe who continuously helped and supported this study. We thank the Banque de Tissus pour la Recherche of the Association Française contre les Myopathies and Dr. Frederic Laude for providing control and FSHD muscle biopsies. We wish to thank Dr. François Leterrier for his continuous interest and active support for this work. We are extremely grateful to Dr. Ned Lamb and Dr. Dominique Mornet for their encouragements. This work was supported by Association Française contre les Myopathies, the Centre National de la Recherche Scientifique and the Muscular Dystrophy Association (MDA3695).

Author information

Authors and Affiliations

  1. Centre de Recherche en Biochimie et Macromoléculaire, FRE-2593-CNRS, 1919 Route de Mende, 34293, Montpellier cedex 5, France

    Dalila Laoudj-Chenivesse & Gilles Carnac

  2. Institut de Génétique Humaine, UPR-CNRS 1142, 141 rue de la Cardonille, 34396, Montpellier, France

    Catherine Bisbal & Anne Fernandez

  3. Institut de Biologie, EA 701, Muscle et pathologie, Faculté de Médecine, Boulevard Henry IV, 34000, Montpellier, France

    Gerald Hugon

  4. Service de Pathologie Générale et de Neuropathologie, Groupe Hospitalier Pellegrin-Enfants, Place Amélie Raba Léon, 33076, Bordeaux cedex, France

    Sandrine Bouillot

  5. Service de Neurology, Hôpital de l’Archet, route de Saint-Antoine de Ginestière, BP 3079, 06202, Nice, France

    Claude Desnuelle

  6. Institut Gustave Roussy, CNRS UMR-1598, 39 rue Camille-Desmoulins, 94805, Villejuif, France

    Yegor Vassetzky

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  1. Dalila Laoudj-Chenivesse
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  2. Gilles Carnac
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  3. Catherine Bisbal
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  4. Gerald Hugon
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  6. Claude Desnuelle
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  8. Anne Fernandez
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Corresponding author

Correspondence to Dalila Laoudj-Chenivesse.

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This work is dedicated to the memory of Dr. Rene Bennes who accompanied it with faith, continuous help, and positive input

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Laoudj-Chenivesse, D., Carnac, G., Bisbal, C. et al. Increased levels of adenine nucleotide translocator 1 protein and response to oxidative stress are early events in facioscapulohumeral muscular dystrophy muscle. J Mol Med 83, 216–224 (2005). https://doi.org/10.1007/s00109-004-0583-7

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