Model System:

Burn

Reference Type:

Journal

Accession No.:

J78266

Journal:


American Journal of Physiology. Endocrinology and Metabolism

Year, Volume, Issue, Page(s):

, 311, 2, E436-E438

Publication Website:

Abstract:

Study explored how hypermetabolism contributes to muscle wasting in burn patients. It was hypothesized that oxidative stress, cytosolic protein degradation, and mitochondrial stress as a result of hypermetabolism contribute to postburn muscle cachexia. Fourteen patients with burns covering more than 30 percent of their total body surface area were studied. Thirteen young healthy adults served as controls. Researchers 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 mitochondrial unfolded protein response (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 and mitochondrial translocases were upregulated, suggesting increased mitochondrial protein degradation and transport of preprotein, respectively. The findings 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. The results suggest a novel role for the mitochondria in burn-induced muscle wasting

Author(s):


Ogunbileje, John O., Porter, Craig, Herndon, David N., Chao, Tony, Abdelrahman, Doaa R., Papadimitriou, Anastasia, Chondronikola, Maria, Zimmers, Teresa A., Reidy, Paul T., Rasmussen, Blake B., Sidossis, Labros S.

Participating Centers: