Increasing O-GlcNAcylation level on organ culture of soleus modulates the calcium activation parameters of muscle fibers. - Université de Lille
Article Dans Une Revue PLoS ONE Année : 2012

Increasing O-GlcNAcylation level on organ culture of soleus modulates the calcium activation parameters of muscle fibers.

Résumé

O-N-acetylglucosaminylation is a reversible post-translational modification which presents a dynamic and highly regulated interplay with phosphorylation. New insights suggest that O-GlcNAcylation might be involved in striated muscle physiology, in particular in contractile properties such as the calcium activation parameters. By the inhibition of O-GlcNAcase, we investigated the effect of the increase of soleus O-GlcNAcylation level on the contractile properties by establishing T/pCa relationships. We increased the O-GlcNAcylation level on soleus biopsies performing an organ culture of soleus treated or not with PUGNAc or Thiamet-G, two O-GlcNAcase inhibitors. The enhancement of O-GlcNAcylation pattern was associated with an increase of calcium affinity on slow soleus skinned fibers. Analysis of the glycoproteins pattern showed that this effect is solely due to O-GlcNAcylation of proteins extracted from skinned biopsies. We also characterized the O-GlcNAcylated contractile proteins using a proteomic approach, and identified among others troponin T and I as being O-GlcNAc modified. We quantified the variation of O-GlcNAc level on all these identified proteins, and showed that several regulatory contractile proteins, predominantly fast isoforms, presented a drastic increase in their O-GlcNAc level. Since the only slow isoform of contractile protein presenting an increase of O-GlcNAc level was MLC2, the effect of enhanced O-GlcNAcylation pattern on calcium activation parameters could involve the O-GlcNAcylation of sMLC2, without excluding that an unidentified O-GlcNAc proteins, such as TnC, could be potentially involved in this mechanism. All these data strongly linked O-GlcNAcylation to the modulation of contractile activity of skeletal muscle.
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Dates et versions

hal-02375641 , version 1 (22-11-2019)
hal-02375641 , version 2 (16-04-2020)
hal-02375641 , version 3 (12-05-2020)

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  • HAL Id : hal-02375641 , version 2
  • PUBMED : 23110217

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Caroline Cieniewski, Valerie Montel, Serge Berthoin, Bruno Bastide. Increasing O-GlcNAcylation level on organ culture of soleus modulates the calcium activation parameters of muscle fibers.. PLoS ONE, 2012, 7, pp.e48218. ⟨hal-02375641v2⟩
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