TAILIEUCHUNG - Báo cáo khoa học: Cardiac ankyrin repeat protein is a marker of skeletal muscle pathological remodelling

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,a-sarcoglycan and dystrophin, respectively). | ỊFEBS Journal Cardiac ankyrin repeat protein is a marker of skeletal muscle pathological remodelling Lydie Laure1 Laurence Suel1 Carinne Roudaut1 Nathalie Bourg1 Ahmed Ouali2 Marc Bartoli1 Isabelle Richard1 and Nathalie Daniele1 1 Genethon-CNRS FRE3087 Evry France 2 INRA de Theix Saint Genes Champanelle France Keywords CARP FoxO1 muscle p21WAF1 CIP1 remodelling Correspondence I. Richard Genethon CNRS FRE3087 1 bis rue de l Internationale 91000 Evry France Fax 33 0 1 60 77 86 98 Tel 33 0 1 69 47 29 38 E-mail richard@ Received 31 July 2008 revised 20 October 2008 accepted 24 November 2008 doi 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 a-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 p21WAF1 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 fasttwitch fibres is observed suggesting that CARP plays a role in .

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