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.