The peculiar apoptotic behavior of skeletal muscle cells

Sara Salucci1, Sabrina Burattini, Valentina Baldassarri

  • 1Department of Earth, Life and Environmental Sciences, University of Urbino, Carlo Bo, Urbino, Italy.

Insights

Skeletal muscle cells (myotubes) are more resistant to apoptosis than myoblasts due to differentiation. Autophagy further protects differentiated muscle cells from cell death stimuli.

Area of Science:

  • Cell Biology
  • Muscle Physiology
  • Apoptosis Research

Background:

  • Apoptosis is crucial for skeletal muscle homeostasis.
  • Deregulation of apoptosis contributes to muscle disorders like sarcopenia and myopathies.

Purpose of the Study:

  • To investigate the in vitro apoptotic response of C2C12 myoblasts versus myotubes.
  • To compare the sensitivity of myoblasts and myotubes to apoptosis-inducing agents: etoposide, staurosporine, and hydrogen peroxide.

Main Methods:

  • Morphological analysis of C2C12 cells.
  • Cytofluorimetric analysis.
  • Confocal microscopy.
  • TUNEL assay.

Main Results:

  • Myotubes exhibited greater resistance to apoptosis than myoblasts across all tested stimuli.
  • Etoposide induced chromatin condensation and DNA fragmentation in myoblasts; myotubes showed coexisting apoptotic and normal nuclei.
  • Staurosporine triggered late apoptosis in myoblasts and secondary necrosis in myotubes.
  • Hydrogen peroxide exposure resulted in poor cell death in myotubes compared to myoblasts.
  • Autophagic granules were abundant in myotubes, suggesting a role in preserving mitochondria and cell integrity.

Conclusions:

  • Skeletal muscle differentiation confers an apoptosis-resistant phenotype to myotubes.
  • Autophagy plays a protective role, enhancing the resistance of C2C12 myotubes to apoptotic stimuli.
  • "Territorial" death domains within the myotube syncytium may contribute to their slower apoptotic response compared to mononucleated cells.

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