Dh. Burgess et al., Human skeletal muscle cytosols are refractory to cytochrome c-dependent activation of type-II caspases and lack APAF-1, CELL DEAT D, 6(3), 1999, pp. 256-261
Apoptotic regulatory mechanisms in skeletal muscle have not been revealed,
This is despite indications that remnant apoptotic events are detected foll
owing exercise, muscle injury and the progression of dystrophinopathies. Th
e recent elicitation of a cytochrome c-mediated induction of caspases has l
ed to speculation regarding a cytochrome c mechanism in muscle, We demonstr
ate that cytosols from skeletal muscle biopsies from healthy human voluntee
rs lack the ability to activate type-it caspases by a cytochrome c-mediated
pathway despite the confirmed presence of both procaspase-3 and -9, This w
as not due to the presence of an endogenous inhibitor, as the muscle cytoso
ls enhanced caspase activity when added to a control cytosol, subsequently
activated by cytochrome c and dATP, In addition, we demonstrate that muscle
cytosols lack the apoptosis protease activator protein-1 (APAF-1), both at
the protein and mRNA levels. These data indicate that human skeletal muscl
e cells will be refractory to mitochondrial-mediated events leading to apop
tosis and thus can escape a major pro-apoptotic regulatory mechanism. This
may reflect an evolutionary adaptation of cell survival in the presence of
the profusion of mitochondria required for energy generation in motility.