Apoptosis and death receptor signaling in diaphragm of burnt rats.
J Surg Res
; 203(1): 6-14, 2016 06 01.
Article
em En
| MEDLINE
| ID: mdl-27338528
ABSTRACT
BACKGROUND:
Respiratory dysfunction is a frequent complication after severe burn injury. Respiratory muscle atrophy may induce respiratory dysfunction due to insufficient inspiratory motive power. Accumulated evidence suggests that apoptosis is very important in skeletal muscle atrophy in multiple pathologic conditions. Therefore, we hypothesize that myonuclear apoptosis contributes to diaphragm atrophy induced by burn injury, and death receptor signaling activation plays a role in this process.METHODS:
Wistar rats in the burn-injured group were subjected to a full-thickness scald injury around 40% of total body surface area. Diaphragm samples were examined for myonuclear apoptosis by transmission electron microscope, terminal deoxynucleotidyl transferase-mediated nick end labeling assay, and immunohistochemistry for caspase-3. Serum level of apoptotic ligands were assessed by ELISA. Activation of death receptor signaling was examined by Western blotting.RESULTS:
Burn injury resulted in significant reductions of diaphragm muscle mass and myofiber cross-section area. Apoptosis in diaphragm appeared from day 1 and peaked on day 4 after injury. The level of soluble TNF-related apoptosis-inducing ligand and the ratio of Fas ligand to soluble Fas in serum significantly increased after burn injury. In diaphragm of burnt animals, the expressions of proapoptotic proteins, such as cleaved caspase-8, cleaved caspase-3, and Bax-to-Bcl-2 ratio were upregulated, whereas expression of pAkt, an antiapoptotic protein, was downregulated. Immunohistochemistry revealed that the most of the caspase-3 was expressed in myofiber nuclei and their surrounding cytoplasm area in tissue sections.CONCLUSIONS:
Severe burn injury induces myonuclear apoptosis in diaphragm, which could be a contributor to diaphragm muscle atrophy. Activation of death receptor signaling may be a mechanism of apoptosis in diaphragm.Palavras-chave
Texto completo:
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Base de dados:
MEDLINE
Assunto principal:
Queimaduras
/
Diafragma
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Atrofia Muscular
/
Apoptose
/
Receptores de Morte Celular
Limite:
Animals
Idioma:
En
Ano de publicação:
2016
Tipo de documento:
Article