The aim of this study was to assess the activity of nonlysosomal proteolytic systems in skeletal and cardiac muscle during burn-induced hypermetabolism (BHM) in rats. Rats underwent 30% TBSA scald burn or sham injury and were observed for up to 42 days. Body weights and resting energy expenditures were determined weekly. Skeletal (soleus/pectoral) muscle and hearts were harvested on days 0 (=control), 7, 14, 21, and 42 after burn. Calpain, caspase-1, caspase-3/7, caspase-6, caspase-8, caspase-9, and proteasome peptidase activities were measured in tissue extracts. Hypermetabolism developed within 3 weeks after burns, as documented by increased resting energy expenditures and decreased body weights on postburn days 21 to 42 (P < 0.05 vs control). Calpain activities did not show significant alterations. Pan caspase activities increased by time and were significantly increased in skeletal and cardiac muscle extracts during hypermetabolism. Although increases in caspase-1, caspase-8, and caspase-9 activities were predominantly responsible for elevated pan caspase activities in skeletal muscle, increases in caspase-6 activities dominated in the heart. Proteasome peptidase activities in skeletal muscle extracts were not significantly altered. Proteasome peptidase activities in heart extracts increased time dependently and were significantly increased during BHM. Activation of caspase cascades during BHM constitutes a uniform response in skeletal and cardiac muscle and may contribute to enhanced metabolic protein turnover. Activation of myocardial proteasome activities may reflect persistent cardiac stress. Further exploration of caspase cascades and the proteasome as therapeutic targets to influence long-term consequences of BHM appears justified.
From the Departments of *Surgery and †Molecular Pharmacology and Therapeutics, Burn and Shock Trauma Research Institute, Loyola University Chicago, Stritch School of Medicine, Maywood, Illinois.
This research was made possible by a grant that was awarded and administered by the U.S. Army Medical Research and Materiel Command and the Telemedicine & Advanced Technology Research Center at Fort Detrick, MD, under Contract Number W81XWH1110559. The views, opinions, and/or findings contained in this research are those of the authors and do not necessarily reflect the views of the Department of Defense and should not be construed as an official DoD/Army position, policy, or decision unless so designated by other documentation. No official endorsement should be made. This work was also supported in part by National Institutes of Health Grant NIHT32GM008750 and the Dr. Ralph and Marian Falk Medical Research Trust.
Address correspondence to Matthias Majetschak, MD, PhD, Burn and Shock Trauma Research Institute, Loyola University Chicago, Stritch School of Medicine, 2160 S. 1st Avenue, Maywood, IL 60153.