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Article Dans Une Revue FEBS Journal Année : 2009

Cardiac ankyrin repeat protein is a marker of skeletal muscle pathological remodelling

Laurence Suel
Carinne Roudaut
Nathalie Bourg
Marc Bartoli
Nathalie Danièle

Résumé

In an attempt to identify potential therapeutic targets for the correction of muscle wasting, the gene expression of several pivotal proteins involved in protein metabolism was investigated in experimental atrophy induced by transient or definitive denervation, as well as in four animal models of muscular dystrophies (deficient for calpain 3, dysferlin, alpha-sarcoglycan and dystrophin, respectively). The results showed that: (a) the components of the ubiquitin-proteasome pathway are upregulated during the very early phases of atrophy but do not greatly increase in the muscular dystrophy models; (b) forkhead box protein O1 mRNA expression is augmented in the muscles of a limb girdle muscular dystrophy 2A murine model; and (c) the expression of cardiac ankyrin repeat protein (CARP), a regulator of transcription factors, appears to be persistently upregulated in every condition, suggesting that CARP could be a hub protein participating in common pathological molecular pathway(s). Interestingly, the mRNA level of a cell cycle inhibitor known to be upregulated by CARP in other tissues, p21(WAF1/CIP1), is consistently increased whenever CARP is upregulated. CARP overexpression in muscle fibres fails to affect their calibre, indicating that CARP per se cannot initiate atrophy. However, a switch towards fast-twitch fibres is observed, suggesting that CARP plays a role in skeletal muscle plasticity. The observation that p21(WAF1/CIP1) is upregulated, put in perspective with the effects of CARP on the fibre type, fits well with the idea that the mechanisms at stake might be required to oppose muscle remodelling in skeletal muscle.

Dates et versions

hal-01610040 , version 1 (04-10-2017)

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Citer

Lydie Laure, Laurence Suel, Carinne Roudaut, Nathalie Bourg, Ahmed Ouali, et al.. Cardiac ankyrin repeat protein is a marker of skeletal muscle pathological remodelling. FEBS Journal, 2009, 276 (3), pp.669-684. ⟨10.1111/j.1742-4658.2008.06814.x⟩. ⟨hal-01610040⟩
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