Caspase 3 expression correlates with skeletal muscle apoptosis in Duchenneand facioscapulo human muscular dystrophy. A potential target for pharmacological treatment?

Apoptosis was detected in different muscular diseases, including severe dys trophin deficiency, but apoptotic mechanisms are not completely described i n adult skeletal muscle. Studying patients affected by Duchenne muscular dy strophy (DMD) and by facio-scapulo-humeral dystrophy (FSHD) we showed an in crease of apoptotic myonuclei, bax, and bcl-2-positive myofibers. Positive correlation was detected between apoptotic nuclei and bar expression (p < 0 .01). Expression of caspases was analyzed by RNase protection. Caspase tran script was not detected in normal skeletal muscles. DMD muscles expressed c aspase 8, 3, 5, 2, 7 and Granzyme B mRNAs. Low levels of caspase 6, 3, and Granzyme B transcripts were detected in FSHD patients. Tissue levels of cas pase 3 protein significantly correlated with apoptotic myonuclei (p < 0.05) and with bar expression (p < 0.01). In all DMD cases the activity of caspa se 3 was increased, while the FSHD samples were heterogeneous. These data i ndicate that human skeletal muscle fibers, during the dystrophic process, m odulate the expression of caspases and that caspase 3 is involved in myofib er cell death, opening new perspective in the pharmacological treatments of muscular dystrophies, such as the use of caspase inhibitors.