Abstract P070: NEU3 Sialidase Overexpression Activates Cell Survival in Murine Skeletal Myoblasts C2C12 and Protects Them from Hypoxia

Abstract

Membrane-bound sialidase NEU3 increase during skeletal muscle differentiation has been shown to protect myoblasts from apoptosis and drive the differentiation process [1]. Thus, the objective of this study was to assess whether up-regulation of NEU3 would enhance the ability of murine skeletal muscle cells to resist to hypoxia, ultimately opposing cell death. We found that C2C12 myoblasts overexpressing NEU3 (L-NEU3) became highly resistant to 1% oxygen or 200 mM deferoxamine induced hypoxia. Moreover, L-NEU3 myoblasts survived a seven-day treatment of combined hypoxia and low serum (2% horse serum used to induce myoblast differentiation), without any significant cell loss. On the contrary, wild type C2C12 could not resist to these culturing conditions and all died within 48h. Real Time PCR showed NEU3 expression increase during all hypoxic treatments both in C2C12 and L-NEU3 cells, suggesting an endogenous NEU3 activation under these conditions. Moreover, we found that NEU3 over-expression activated pro-survival signalling pathways through up-regulation and activation of EGF receptor. Overall, our data support the hypothesis that NEU3 may play a critical role in the response of skeletal myoblasts to hypoxia and the preservation of cell viability by activating pro-survival signalling pathways. [1] Anastasia L. et al. J.Biol.Chem. 2008, 283 (52): 36265–36271.