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A non-apoptotic role for caspase-9 in muscle differentiation
- Source :
- Journal of cell science. 121(Pt 22)
- Publication Year :
- 2008
-
Abstract
- Caspases, a family of cysteine proteases most often investigated for their roles in apoptosis, have also been demonstrated to have functions that are vital for the efficient execution of cell differentiation. One such role that has been described is the requirement of caspase-3 for the differentiation of skeletal myoblasts into myotubes but, as yet, the mechanism leading to caspase-3 activation in this case remains elusive. Here, we demonstrate that caspase-9, an initiator caspase in the mitochondrial death pathway, is responsible for the activation of caspase-3 in differentiating C2C12 cells. Reduction of caspase-9 levels, using an shRNA construct, prevented caspase-3 activation and inhibited myoblast fusion. Myosin-heavy-chain expression, which accompanies myoblastic differentiation, was not caspase-dependent. Overexpression of Bcl-xL, a protein that inhibits caspase-9 activation, had the same effect on muscle differentiation as knockdown of caspase-9. These data suggest that the mitochondrial pathway is required for differentiation; however, the release of cytochrome c or Smac (Diablo) could not be detected, raising the possibility of a novel mechanism of caspase-9 activation during muscle differentiation.
- Subjects :
- fusion
family
muscle
Cellular differentiation
Myoblasts, Skeletal
bcl-xl
release
caspase-9
cytochrome-c
Cell Line
Myoblast fusion
Mice
expression
Myocyte
Animals
skeletal-muscle
Caspase
Caspase-9
active caspases
biology
Myogenesis
Caspase 3
apoptosis
Cell Differentiation
Cell Biology
differentiation
cell-death
Caspase 9
Cell biology
mitochondria
Enzyme Activation
Apoptosis
shrna
biology.protein
activation
RNA Interference
C2C12
Subjects
Details
- ISSN :
- 00219533
- Volume :
- 121
- Issue :
- Pt 22
- Database :
- OpenAIRE
- Journal :
- Journal of cell science
- Accession number :
- edsair.doi.dedup.....3c29caf052e857756378314cb1b01795