Polyamines support myogenesis by facilitating myoblast migration

Abstract

ABSTRACTThe regeneration of the muscle tissue relies on the differentiation of myoblasts into myocytes, to create myotubes and myofibers. Disruption of key events in this process may interfere with the correct formation or repair of muscle tissue. Polyamines, ubiquitous polycations that are essential for fundamental cellular processes, were demonstrated necessary for myogenesis; however, the mechanism by which polyamines contribute to this process has not yet been deciphered. In the present study, we examined the effect of polyamine depletion on the muscle regeneration model of C2C12 myoblasts. Our results reveal a requirement for polyamines at the very beginning of the muscle differentiation process. Myogenesis is accompanied by polyamine synthesis, even though the myoblasts contain high levels of polyamines at the moment of induction. Polyamine depletion at the time of induction, or inability to synthesize more polyamines during the first 24 hours of the process, inhibited myogenesis. Polyamine depletion inhibited the expression of all tested myogenic markers (Pax7, MyoD, Myogenin, Myf5 and Myosin heavy chain), as well as the cells migration and fusion abilities. Real time PCR analysis revealed two key early activation and migration factors, HGF and Annexin A1.