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.

[1]  W. Mitch,et al.  Nutrition in CAPD: serum bicarbonate and the ubiquitin-proteasome system in muscle. , 2002, Kidney international.

[2]  W. Mitch,et al.  ENaC Degradation in A6 Cells by the Ubiquitin-Proteosome Proteolytic Pathway* , 2001, The Journal of Biological Chemistry.

[3]  W. Mitch,et al.  Transcription factors and muscle cachexia: is there a therapeutic target? , 2001, The Lancet.

[4]  W. Mitch,et al.  Glucocorticoids Induce Proteasome C3 Subunit Expression in L6 Muscle Cells by Opposing the Suppression of Its Transcription by NF-κB* , 2000, The Journal of Biological Chemistry.

[5]  Claudine Jurkovitz,et al.  Evaluation of signals activating ubiquitin-proteasome proteolysis in a model of muscle wasting. , 1999, American journal of physiology. Cell physiology.

[6]  A. Goldberg,et al.  Muscle protein breakdown and the critical role of the ubiquitin-proteasome pathway in normal and disease states. , 1999, The Journal of nutrition.

[7]  Y. Lazebnik,et al.  Caspases: enemies within. , 1998, Science.

[8]  F. Scolari,et al.  Correction of metabolic acidosis increases serum albumin concentrations and decreases kinetically evaluated protein intake in haemodialysis patients: a prospective study. , 1998, Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association.

[9]  J. Walls,et al.  Role of an improvement in acid-base status and nutrition in CAPD patients. , 1997, Kidney international.

[10]  A. Manatunga,et al.  Mechanisms permitting nephrotic patients to achieve nitrogen equilibrium with a protein-restricted diet. , 1997, The Journal of clinical investigation.

[11]  S. Downie,et al.  Correction of acidosis in hemodialysis decreases whole-body protein degradation. , 1997, Journal of the American Society of Nephrology : JASN.

[12]  A. Goldberg,et al.  Mechanisms of muscle wasting. The role of the ubiquitin-proteasome pathway. , 1996, The New England journal of medicine.

[13]  A. Goldberg,et al.  Importance of the ATP-Ubiquitin-Proteasome Pathway in the Degradation of Soluble and Myofibrillar Proteins in Rabbit Muscle Extracts* , 1996, The Journal of Biological Chemistry.

[14]  L. Phillips,et al.  Muscle wasting in insulinopenic rats results from activation of the ATP-dependent, ubiquitin-proteasome proteolytic pathway by a mechanism including gene transcription. , 1996, The Journal of clinical investigation.

[15]  S. Downie,et al.  Correction of acidosis in CAPD decreases whole body protein degradation. , 1996, Kidney international.

[16]  W. Mitch,et al.  The acidosis of chronic renal failure activates muscle proteolysis in rats by augmenting transcription of genes encoding proteins of the ATP-dependent ubiquitin-proteasome pathway. , 1996, The Journal of clinical investigation.

[17]  W. Mitch,et al.  Protein degradation and increased mRNAs encoding proteins of the ubiquitin-proteasome proteolytic pathway in BC3H1 myocytes require an interaction between glucocorticoids and acidification. , 1996, Proceedings of the National Academy of Sciences of the United States of America.

[18]  M. McNurlan,et al.  Chronic metabolic acidosis decreases albumin synthesis and induces negative nitrogen balance in humans. , 1995, The Journal of clinical investigation.

[19]  A. Goldberg,et al.  Inhibitors of the proteasome block the degradation of most cell proteins and the generation of peptides presented on MHC class I molecules , 1994, Cell.

[20]  G. Deferrari,et al.  Skeletal muscle protein synthesis and degradation in patients with chronic renal failure. , 1994, Kidney international.

[21]  A. Goldberg,et al.  Metabolic acidosis stimulates muscle protein degradation by activating the adenosine triphosphate-dependent pathway involving ubiquitin and proteasomes. , 1994, The Journal of clinical investigation.

[22]  B. Pereira,et al.  Plasma levels of IL-1β, TNFα and their specific inhibitors in undialyzed chronic renal failure, CAPD and hemodialysis patients , 1994 .

[23]  A. Goldberg,et al.  Glucocorticoids activate the ATP-ubiquitin-dependent proteolytic system in skeletal muscle during fasting. , 1993, The American journal of physiology.

[24]  C. Scrimgeour,et al.  Ammonium chloride-induced acidosis increases protein breakdown and amino acid oxidation in humans. , 1992, The American journal of physiology.

[25]  R. Hoerr,et al.  Adaptation to low-protein diets in renal failure: leucine turnover and nitrogen balance. , 1990, Journal of the American Society of Nephrology : JASN.

[26]  W. Mitch,et al.  Mechanisms for defects in muscle protein metabolism in rats with chronic uremia. Influence of metabolic acidosis. , 1987, The Journal of clinical investigation.

[27]  M. Mcgeown,et al.  The effect of the correction of metabolic acidosis on nitrogen and potassium balance of patients with chronic renal failure. , 1984, The American journal of clinical nutrition.