Hypermetabolism and hypercatabolism of skeletal muscle accompany mitochondrial stress following severe burn trauma.
Am J Physiol Endocrinol Metab
; 311(2): E436-48, 2016 08 01.
Article
em En
| MEDLINE
| ID: mdl-27382037
ABSTRACT
Burn trauma results in prolonged hypermetabolism and skeletal muscle wasting. How hypermetabolism contributes to muscle wasting in burn patients remains unknown. We hypothesized that oxidative stress, cytosolic protein degradation, and mitochondrial stress as a result of hypermetabolism contribute to muscle cachexia postburn. Patients (n = 14) with burns covering >30% of their total body surface area were studied. Controls (n = 13) were young healthy adults. We found that burn patients were profoundly hypermetabolic at both the skeletal muscle and systemic levels, indicating increased oxygen consumption by mitochondria. In skeletal muscle of burn patients, concurrent activation of mTORC1 signaling and elevation in the fractional synthetic rate paralleled increased levels of proteasomes and elevated fractional breakdown rate. Burn patients had greater levels of oxidative stress markers as well as higher expression of mtUPR-related genes and proteins, suggesting that burns increased mitochondrial stress and protein damage. Indeed, upregulation of cytoprotective genes suggests hypermetabolism-induced oxidative stress postburn. In parallel to mtUPR activation postburn, mitochondrial-specific proteases (LONP1 and CLPP) and mitochondrial translocases (TIM23, TIM17B, and TOM40) were upregulated, suggesting increased mitochondrial protein degradation and transport of preprotein, respectively. Our data demonstrate that proteolysis occurs in both the cytosolic and mitochondrial compartments of skeletal muscle in severely burned patients. Increased mitochondrial protein turnover may be associated with increased protein damage due to hypermetabolism-induced oxidative stress and activation of mtUPR. Our results suggest a novel role for the mitochondria in burn-induced cachexia.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Consumo de Oxigênio
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Queimaduras
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Caquexia
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RNA Mensageiro
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Estresse Oxidativo
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Músculo Esquelético
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Mitocôndrias Musculares
Tipo de estudo:
Etiology_studies
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Observational_studies
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Risk_factors_studies
Idioma:
En
Revista:
Am J Physiol Endocrinol Metab
Assunto da revista:
ENDOCRINOLOGIA
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FISIOLOGIA
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METABOLISMO
Ano de publicação:
2016
Tipo de documento:
Article