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Immunolabelling Myofiber Degeneration in Muscle Biopsies
06:37

Immunolabelling Myofiber Degeneration in Muscle Biopsies

Published on: December 5, 2019

Skeletal muscle myocytes undergo protein loss and reactive oxygen-mediated NF-kappaB activation in response to tumor

Y P Li1, R J Schwartz, I D Waddell

  • 1Department of Medicine, Baylor College of Medicine, Houston, Texas 77030, USA.

FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology
|July 10, 1998
PubMed

Insights

Tumor necrosis factor alpha (TNF-alpha) directly causes skeletal muscle protein loss by activating nuclear factor kappaB (NF-kappaB) signaling. This process involves reactive oxygen species and leads to muscle atrophy in chronic diseases.

Area of Science:

  • Cellular biology
  • Molecular biology
  • Physiology

Background:

  • Skeletal muscle atrophy is linked to chronic diseases and tumor necrosis factor alpha (TNF-alpha).
  • The direct impact of TNF-alpha on differentiated muscle cells and its signaling pathways remain unclear.

Purpose of the Study:

  • To investigate the direct effects of TNF-alpha on differentiated skeletal muscle cells.
  • To elucidate the signaling mechanisms underlying TNF-alpha-induced muscle atrophy.

Main Methods:

  • Utilized mouse C2C12 myotubes and primary rat skeletal muscle cultures.
  • Administered TNF-alpha and measured protein content, myosin heavy chain (MHCf) levels, DNA content, and MHCf synthesis.
  • Assessed nuclear factor kappaB (NF-kappaB) activation, I-kappaBalpha degradation, and ubiquitin conjugation.
  • Employed proteasome inhibitor (MG132) and catalase to explore signaling pathways and reactive oxygen species involvement.

Main Results:

  • TNF-alpha induced dose- and time-dependent reductions in total protein and MHCf content in differentiated myotubes.
  • These effects occurred at low TNF-alpha concentrations without altering DNA content or MHCf synthesis.
  • TNF-alpha activated NF-kappaB binding and stimulated I-kappaBalpha degradation, indicating NF-kappaB pathway activation.
  • Reactive oxygen species (ROS) mediate TNF-alpha's activation of NF-kappaB and I-kappaBalpha degradation, as shown by catalase inhibition and hydrogen peroxide's effects.

Conclusions:

  • TNF-alpha directly causes skeletal muscle protein loss in differentiated cells.
  • NF-kappaB signaling is rapidly activated by TNF-alpha in skeletal muscle.
  • The TNF-alpha/NF-kappaB pathway in skeletal muscle is regulated by endogenous reactive oxygen species.
Keywords:
Non-programmatic

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