Oxidative stress is required for mechanical ventilation-induced protease activation in the diaphragm.
J Appl Physiol (1985)
; 108(5): 1376-82, 2010 May.
Article
en En
| MEDLINE
| ID: mdl-20203072
ABSTRACT
Prolonged mechanical ventilation (MV) results in diaphragmatic weakness due to fiber atrophy and contractile dysfunction. Recent work reveals that activation of the proteases calpain and caspase-3 is required for MV-induced diaphragmatic atrophy and contractile dysfunction. However, the mechanism(s) responsible for activation of these proteases remains unknown. To address this issue, we tested the hypothesis that oxidative stress is essential for the activation of calpain and caspase-3 in the diaphragm during MV. Cause-and-effect was established by prevention of MV-induced diaphragmatic oxidative stress using the antioxidant Trolox. Treatment of animals with Trolox prevented MV-induced protein oxidation and lipid peroxidation in the diaphragm. Importantly, the Trolox-mediated protection from MV-induced oxidative stress prevented the activation of calpain and caspase-3 in the diaphragm during MV. Furthermore, the avoidance of MV-induced oxidative stress not only averted the activation of these proteases but also rescued the diaphragm from MV-induced diaphragmatic myofiber atrophy and contractile dysfunction. Collectively, these findings support the prediction that oxidative stress is required for MV-induced activation of calpain and caspase-3 in the diaphragm and are consistent with the concept that antioxidant therapy can retard MV-induced diaphragmatic weakness.
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Respiración Artificial
/
Diafragma
/
Calpaína
/
Estrés Oxidativo
/
Debilidad Muscular
/
Caspasa 3
Tipo de estudio:
Prognostic_studies
Límite:
Animals
Idioma:
En
Revista:
J Appl Physiol (1985)
Asunto de la revista:
FISIOLOGIA
Año:
2010
Tipo del documento:
Article
País de afiliación:
Estados Unidos