The daily turnover of cellular proteins is large, with amounts equivalent t
o the protein contained in 1.0 to 1.5 kg of muscle. Consequently, even a sm
all, persistent increase in the rate of protein degradation or decrease in
protein synthesis will result in substantial loss of muscle mass. Activatio
n of protein degradation in the ubiquitin-proteasome system is the mechanis
m contributing to loss of muscle mass in kidney disease. Because other cata
bolic conditions also stimulate this system to cause loss of muscle mass, t
he identification of activating signals is of interest. A complication of k
idney disease, metabolic acidosis, activates this system in muscle by a pro
cess that requires glucocorticoids. The influence of inflammatory cytokines
on this system in muscle is more complicated, as evidence indicates that c
ytokines suppress the system, but glucocorticoids block the effect of cytok
ines to slow protein breakdown in the system. New information identifying m
echanisms that activate protein breakdown and the rebuilding of muscle fibe
rs would lead to therapies that successfully prevent the loss of muscle mas
s in kidney disease and other catabolic illnesses. (C) 2001 by the National
Kidney Foundation, Inc.