Expression patterns of initiator and effector caspases in denervated human skeletal muscle.
Muscle Nerve
; 31(2): 175-81, 2005 Feb.
Article
en En
| MEDLINE
| ID: mdl-15625686
ABSTRACT
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.
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Bases de datos:
MEDLINE
Asunto principal:
Regulación Enzimológica de la Expresión Génica
/
Músculo Esquelético
/
Caspasas
Límite:
Adult
/
Aged
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Female
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Humans
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Male
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Middle aged
Idioma:
En
Revista:
Muscle Nerve
Año:
2005
Tipo del documento:
Article
País de afiliación:
Alemania