Abstract:
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Communication n° 59. Alterations in the neural message could result in transformations of muscle phenotype and contractile properties via post-translational modifications. Here, we studied two types of modifications: the O-linked N-acetylglucosaminylation (O-GlcNAc) after 15 days of hypodynamia-hypokinesia (HH), and the MLC2 (Myosin Light Chain2) phosphorylation (known to modulate the actomyosin interaction) after 15 days of HH or denervation (DE). Both models alter the neural command and induce slow-to-fast transformations of the slow soleus muscle by overexpressions of MHC and MLC fast isoforms. The fast EDL muscle underwent fast-to-slow transitions after DE but remains unchanged after HH. In soleus, DE and HH provoked an increased MLC2 phosphorylation. In EDL, only DE decreased MLC2 phosphorylation. Calcineurine-NFAT (CaN-NFAT) pathway has a role in the activation of the genes specific to slow phenotype by a nervous discharge (slow pattern). We also studied the effects of cyclosporine A (CsA, CaN inhibitor) on muscle phenotype and MLC2 phosphorylation. CsA induced slow-to-fast transitions in soleus and fast-to-slow transitions in EDL, with no change in phosphorylation. The increase in phosphorylation accompanying slow-to-fast transition did not seem to be CaN-NFAT dependent. The O-GlcNAc level of the contractile proteins was modified after HH with a significant decrease in soleus and increase in EDL. We identified key contractile proteins as well as enzyme involved in the energetic metabolism as O-GlcNAc. The parallel increase in O-GlcNAc level and HSP 70 expression mesured in EDL after HH led us to suggest a putative role of glycosylation in the modulation of the atrophy. Moreover, we demontrate a modulation of the calcium sensitivity of skeletal muscle fibers by O-GlcNAc. Our results suggested that an alteration of the neural command induced a modification of the muscle phenotype associated to post-translational modifications. The variations of O-GlcNAc level supposed an implication of this modification in muscle physiology and a possible interplay with phosphorylation.
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