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

M. Sandri, A. H. El Meslemani, C. Sandri, P. Schjerling, K. Vissing, J. L. Andersen, K. Rossini, Ugo Carraro, C. Angelini

Research output: Contribution to journalArticle

Abstract

Apoptosis was detected in different muscular diseases, including severe dystrophin deficiency, but apoptotic mechanisms are not completely described in adult skeletal muscle. Studying patients affected by Duchenne muscular dystrophy (DMD) and by facio-scapulo-humeral dystrophy (FSHD) we showed an increase of apoptotic myonuclei, bax. and bcl-2-positive myofibers. Positive correlation was detected between apoptotic nuclei and bax expression (p <0.01), Expression of caspases was analyzed by RNase protection. Caspase transcript was not detected in normal skeletal muscles. DMD muscles expressed caspase 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 caspase 3 protein significantly correlated with apoptotic myonuclei (p <0.05) and with bax expression (p <0.01). In all DMD cases the activity of caspase 3 was increased, while the FSHD samples were heterogeneous. These data indicate that human skeletal muscle fibers, during the dystrophic process, modulate the expression of caspases and that caspase 3 is involved in myofiber cell death, opening new perspective in the pharmacological treatments of muscular dystrophies, such as the use of caspase inhibitors.

Original languageEnglish
Pages (from-to)302-312
Number of pages11
JournalJournal of Neuropathology and Experimental Neurology
Volume60
Issue number3
Publication statusPublished - 2001

Keywords

  • Apoptosis
  • Caspase
  • Dystrophy
  • Skeletal muscle

ASJC Scopus subject areas

  • Pathology and Forensic Medicine
  • Neuroscience(all)

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    Sandri, M., El Meslemani, A. H., Sandri, C., Schjerling, P., Vissing, K., Andersen, J. L., Rossini, K., Carraro, U., & Angelini, C. (2001). Caspase 3 expression correlates with skeletal muscle apoptosis in Duchenne and facioscapulo human muscular dystrophy. A potential target for pharmacological treatment? Journal of Neuropathology and Experimental Neurology, 60(3), 302-312.