Elsevier

Journal of Surgical Research

Volume 93, Issue 1, September 2000, Pages 120-126
Journal of Surgical Research

Regular Article
Insulin Suppresses the Increased Activities of Lysosomal Cathepsins and Ubiquitin Conjugation System in Burn-Injured Rats

https://doi.org/10.1006/jsre.2000.5958Get rights and content

Abstract

Background. Burn injury results in increased rate of skeletal muscle protein degradation. In vitro studies on incubated muscles indicate that increased rate of protein degradation is due to activation of multiple proteolytic systems, but the supporting evidence is of an indirect nature. The present study was carried out to investigate the role of various lysosomal cathepsins, ubiquitin conjugation, and proteasome systems in accelerated proteolysis, and the effect of insulin in burn-induced muscle wasting syndrome.

Materials and methods. Fifteen to twenty percent total body surface area scald burn injury was inflicted on the shaved dorsum of young growing rats. Insulin-treated rats received a daily single subcutaneous injection for 3 days (0.25–1.0 U/day). The rate of ubiquitin conjugation to endogenous proteins and exogenously added 125I-lysozyme and the activities of various proteases were measured in muscle homogenates.

Results. Burn injury resulted in increased rate of ubiquitin conjugation to endogenous proteins and 125I-lysozyme. Activities of cathepsins B, C, H, and L were also up-regulated following burn injury. When the burn-injured rats were treated with insulin, the increased rate of ubiquitin conjugation and cathepsin activities were suppressed to the control levels.

Conclusions. The increased ubiquitin conjugation and lysosomal cathepsins contribute to accelerated protein degradation in burn-injured rats and insulin suppresses the muscle protein degradation at least in part by suppressing the activities of lysosomal cathepsins and of ubiquitin conjugation system.

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    To whom correspondence should be addressed at Shriners Burns Hospital, 51 Blossom Street, Boston, MA 02114. Fax: (617) 371-4950. E-mail: [email protected].

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