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Published on: May 17, 2016

TNFalpha inhibits skeletal myogenesis through a PW1-dependent pathway by recruitment of caspase pathways

Dario Coletti1, Ellen Yang, Giovanna Marazzi

  • 1Department of Biochemistry and Molecular Biology, Mount Sinai School of Medicine, 1 Gustave Levy Place, New York, NY 10029, USA.

The EMBO Journal
|February 16, 2002
PubMed

Insights

Tumor necrosis factor-alpha (TNFalpha) inhibits muscle differentiation by activating caspases, independent of NFkappaB. This novel pathway involves PW1 and BAX, crucial for TNFalpha

Area of Science:

  • Cell Biology
  • Molecular Biology
  • Muscle Physiology

Background:

  • Cachexia, linked to poor prognosis in chronic diseases, involves Tumor Necrosis Factor-alpha (TNFalpha) in skeletal muscle wasting.
  • TNFalpha is known to inhibit skeletal muscle differentiation, with proposed mechanisms involving NFkappaB and MyoD downregulation.
  • The precise molecular mechanisms of TNFalpha's effects on skeletal muscle remain incompletely understood.

Purpose of the Study:

  • To elucidate a novel pathway by which TNFalpha inhibits skeletal muscle differentiation.
  • To investigate the roles of caspases, PW1, NFkappaB, and BAX in TNFalpha-mediated inhibition of myogenesis.

Main Methods:

  • Investigated TNFalpha's effects on skeletal muscle differentiation in vitro.
  • Analyzed the involvement of caspases, PW1, NFkappaB, and BAX in TNFalpha signaling.
  • Utilized bax-deficient myoblasts to assess the role of BAX in TNFalpha-induced effects.

Main Results:

  • TNFalpha inhibits muscle differentiation via caspase activation, independent of apoptosis and NFkappaB activation.
  • This process is dependent on the expression of PW1.
  • BAX-deficient myoblasts did not activate caspases and differentiated normally in the presence of TNFalpha, indicating a BAX-dependent mechanism.

Conclusions:

  • TNFalpha inhibits myogenesis through a novel pathway involving PW1 and BAX-dependent caspase activation.
  • This mechanism recruits components of apoptotic pathways to block muscle differentiation.
  • Findings reveal a new understanding of TNFalpha's role in muscle wasting and disease.

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