Pharmacologic inhibition of c-Abl alters myogenesis in C2C12 cells

Fabian J. Montecino; Alvarez, Alejandra; OlguÍn, Hugo CÉsar


Introduction: the non-receptor tyrosine kinase c-Abl, is key for multiple cellular processes including proliferation, survival, apoptosis and differentiation among others. In the context of myogenesis, c-Abl it’s necessary for myoblasts differentiation via interaction with Cdo, a multifunctional membrane receptor, inducing the activation of p38α/β MAPK pathway. Furthermore, this kinase regulates the activity of the transcription factor MyoD during DNAdamage stress response, pausing differentiation. However, it’s not clear if c-Abl modulates key myogenic transcription factors (e.g. Pax7, myogenin, MyoD) during normal myogenic progression. The objective of this work is to determine if c-Abl inhibition alters the expression levels of Pax7 and MyoD, affecting therefore, muscle differentiation. Materials & Methods: expression of Pax7 and MyoD was analyzed by western blot, RT-PCR and immunofluorescence in C2C12 cells treated with Imatinib (c-Abl competitive inhibitor) or vehicle. Phase contrast and immunofluorescence microscopy was used for the analysis of marker expression and morphological differentiation. Results: the levels of Pax7 and MyoD proteins decreased in cells treated with Imatinib, when compared with cells treated with vehicle. On other hand, RNA levels for these proteins remained unchanged. Finally, we observed that differentiation process was altered in C2C12 cells treated with c-Abl inhibitor. Discussion: this data suggest that c-Abl could regulate the myogenic progression, modulating Pax7 and MyoD.

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Fecha de publicación: 2016
Año de Inicio/Término: Octubre
Idioma: Inglés