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Expression patterns of initiator and effector caspases in denervated human skeletal muscle
Author(s) -
Tews Dominique S.,
Behrhof Wera,
Schindler Susanne
Publication year - 2005
Publication title -
muscle and nerve
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.025
H-Index - 145
eISSN - 1097-4598
pISSN - 0148-639X
DOI - 10.1002/mus.20253
Subject(s) - caspase , apoptosis , downregulation and upregulation , microbiology and biotechnology , atrophy , muscle atrophy , biology , caspase 3 , caspase 9 , programmed cell death , denervation , caspase 8 , skeletal muscle , myocyte , endocrinology , biochemistry , genetics , gene
There is evidence that apoptotic cell death contributes to the loss of denervated muscle fibers. In 17 patients with neurogenic muscular atrophy, we studied the expression of the apoptosis mediators APAF‐1/caspase‐9 and degrading caspases‐2, ‐3, and ‐7 by immunohistochemical and western blot analyses. Muscle with neurogenic atrophy showed distinct upregulation of caspase‐9 and ‐7 and no expression for APAF‐1 (apoptosis protease‐activating factor‐1) and caspase‐2 and ‐3. Expression of caspase‐7 was restricted to atrophic fibers, but caspase‐9 was also found in normal‐sized muscle fibers where its expression was often confined to single fiber segments. These findings indicate that upregulated expression of caspase‐9 can initiate the proteolytic cascade involving the downstream executioner caspase‐7, which mediates degradation of denervated muscle fibers. However, apoptotic events may be restricted to single muscle‐fiber segments, where apoptotic cell degradation contributes to the long‐term process of atrophy. Pharmacological inhibition of caspases may be a therapeutic strategy in diminishing muscle atrophy. Muscle Nerve, 2005