Mechanisms activating proteolysis to cause muscle atrophy in catabolic conditions.
The daily turnover of cellular proteins is the same as the amount of protein contained in 1 to 1.5 kg of muscle. Consequently, even a small but persistent increase in protein degradation or decrease in protein synthesis results in substantial loss of muscle mass, as shown in patients with trauma, sepsis, or kidney failure. Activation of the ubiquitin-proteasome proteolytic system in muscle is the major pathway contributing to loss of muscle mass in catabolic illnesses. At least 3 signals have been identified as causing loss of muscle mass: acidosis, defective insulin action, and glucocorticoids. The influence of inflammatory cytokines on this system in muscle is more complicated because cytokines can suppress the system unless glucocorticoids are present. An initial reaction that breaks down muscle appears to involve caspases. Such information could lead to therapies that successfully prevent the loss of muscle mass in catabolic illnesses.
Mitch
William E
WE
Department of Medicine, University of Texas, Galveston, Galveston, TX 77555, USA.
Price
S Russ
SR
D000138:Acidosis / Q000503:physiopathology; D000818:Animals; D003546:Cysteine Endopeptidases / Q000378:metabolism; D010450:Endopeptidases / Q000378:metabolism*; D005938:Glucocorticoids / Q000502:physiology; D006801:Humans; D007249:Inflammation / Q000503:physiopathology; D009097:Multienzyme Complexes / Q000378:metabolism; D009124:Muscle Proteins / Q000378:metabolism*; D009133:Muscular Atrophy / Q000209:etiology*; D046988:Proteasome Endopeptidase Complex; D051437:Renal Insufficiency / Q000150:complications; D018805:Sepsis / Q000150:complications; D025801:Ubiquitin / Q000378:metabolism; D014947:Wounds and Injuries / Q000150:complications
D005938:Glucocorticoids; D009097:Multienzyme Complexes; D009124:Muscle Proteins; D025801:Ubiquitin; D010450:Endopeptidases; D003546:Cysteine Endopeptidases; D046988:Proteasome Endopeptidase Complex