Mechanisms causing muscle proteolysis in uremia: The influence of insulin and cytokines

Decreased muscle mass in patients with chronic renal failure (CRF) can be c aused by mechanisms that activate the ubiquitin-proteasome proteolytic syst em. This system accelerates the degradation of muscle protein. Concurrent w ith muscle protein breakdown, there is an increase in transcription of gene s encoding components of this pathway, including ubiquitin and subunits of the proteasome. Potential activating signals include meta bolic acidosis wh ich stimulates proteolysis in CRF patients and in muscle of rats with CRF b y a mechanism involving glucocorticoids. In CRF patients, there is insulin resistance and high circulating levels of tumor necrosis factor and other c ytokines. As the ubiquitin proteasome proteolytic system is activated in ac ute diabetes and in catabolic conditions associated with high levels of cir culating cytokines, these factors could also activate this pathway. Consequ ently, we examined whether the transcription factor activated by certain cy tokines, NF-kappa B, is involved in the transcriptional regulation of subun its of the 265 proteasome complex. The results suggest that cytokines may b e involved in the regulation of muscle protein degradation in uremia. Copyr ight (C) 2000 S. Karger AG, Basel.