Document Type
Article
Publication Date
12-1-2006
Publication Title
Apoptosis
Disciplines
Biology
Abstract
Apoptosis rather than differentiation is a physiological process during myogenesis and muscle regeneration. When cultured myoblasts were induced to differentiate, we detected an increase in caspase 8 activity. Pharmacological inhibition of caspase 8 activity decreased apoptosis. Expression of a dominant-negative mutant of the adapter protein FADD also abrogated apoptosis, implicating a death ligand pathway. Treatment with TRAIL, but not Fas, induced apoptosis in these myoblasts. Accordingly, treatment with a soluble TRAIL decoy receptor or expression of a dominant-negative mutant of the TRAIL receptor DR5 abrogated apoptosis. While TRAIL expression levels remained unaltered in apoptotic myoblasts, DR5 expression levels increased. Finally, we also detected a reduction in FLIP, a death-receptor effector protein and caspase 8 competitive inhibitor, to undetectable levels in apoptotic myoblasts. Thus, our data demonstrate an important role for the TRAIL/DR5/FADD/caspase 8 pathway in the apoptosis associated with skeletal myoblast differentiation. Identifying the functional apoptotic pathways in skeletal myoblasts may prove useful in minimizing the myoblast apoptosis that contributes pathologically to a variety of diseases and in minimizing the apoptosis of transplanted myoblasts to treat these and other disease states. © 2006 Springer Science + Business Media, LLC.
DOI
10.1007/s10495-006-0196-4
Version
Publisher's PDF
Recommended Citation
O'Flaherty, J.; Mei, Y.; Freer, M.; and Weyman, C. M., "Signaling Through the TRAIL Receptor DR5/FADD Pathway Plays a Role in the Apoptosis Associated With Skeletal Myoblast Differentiation" (2006). Biological, Geological, and Environmental Faculty Publications. 237.
https://engagedscholarship.csuohio.edu/scibges_facpub/237
Creative Commons License
This work is licensed under a Creative Commons Attribution 4.0 International License.
Volume
11
Issue
12
