Critical illness myopathy (CIM) is associated with severe
muscle atrophy and
fatigue in affected patients. Apoptotic signaling is involved in
atrophy and is elevated in muscles from patients with CIM. In this study we investigated underlying mechanisms of apoptosis-related pathways in muscles with different fiber type composition in a rat model of CIM using
denervation and
glucocorticoid administration (
denervation and
steroid-induced
myopathy, DSIM). Soleus and tibialis anterior (TA) muscles showed severe
muscle atrophy (40-60% of control muscle weight) and significant apoptosis in interstitial as well as myofiber nuclei that was similar between the two muscles with DSIM.
Caspase-3 and -8 activities, but not
caspase-9 and -12, were elevated in TA and not in soleus muscle, while the
caspase-independent
proteins endonuclease G (EndoG) and
apoptosis inducing factor (AIF) were not changed in abundance nor differentially localized in either muscle.
Anti-apoptotic proteins HSP70, -27, and apoptosis repressor with a caspase recruitment domain (
ARC) were elevated in soleus compared to TA muscle and
ARC was significantly decreased with induction of DSIM in soleus. Results indicate that apoptosis is a significant process associated with DSIM in both soleus and TA muscles, and that apoptosis-associated processes are differentially regulated in muscles of different function and fiber type undergoing
atrophy due to DSIM. We conclude that interventions combating apoptosis with CIM may need to be directed towards inhibiting
caspase-dependent as well as -independent mechanisms to be able to affect muscles of all fiber types.