The Gene Expression of Ubiquitin Ligase E3α Is Upregulated in Skeletal Muscle during Sepsis in Rats—Potential Role of Glucocorticoids

Abstract

Muscle protein breakdown during sepsis is associated with upregulated expression and activity of the ubiquitin-proteasome proteolytic pathway. Previous studies suggest that ubiquitination of proteins in skeletal muscle is regulated by the ubiquitin ligase E3α together with the 14 kDa ubiquitin-conjugating enzyme E214k. The E3α gene was cloned only recently. The influence of sepsis on the gene expression of E3α in skeletal muscle has not been reported. In the present study, induction of sepsis in rats by cecal ligation and puncture resulted in increased mRNA levels for E3α in white, fast-twitch but not in red slow-twitch muscle. Treatment with the glucocorticoid receptor antagonist RU38486 (10 mg/kg) prevented the sepsis-induced increase in E3α and E214k mRNA levels. The present study is the first report of increased E3α expression in skeletal muscle during sepsis. The results lend further support to the concept that glucocorticoid-mediated upregulation of the ubiquitin-proteasome proteolytic pathway is involved in sepsis-induced muscle cachexia. Increased expression of both E3α and E214k suggests that muscle proteins are degraded in the N-end rule pathway during sepsis.