Mechanisms causing muscle wasting in uraemia: From cultured cells to patients

摘要

Summary:Loss of muscle mass is a common problem in patients with acute or chronic renal failure. the mechanisms causing this problem involve blocking the metabolic responses that must be activated to maintain protein balance whenever protein intake is reduced (e.g. by anorexia or for other reasons). In uraemia, the ability to reduce degradation of essential amino acids or protein is blocked and muscle protein is lost; the signal is metabolic acidosis. In cultured myocytes, isolated muscles and patients, acidification increases the degradation of branched‐chain amino acids and protein. This response requires glucocorticoids and involves stimulation of the activity of specific enzymes, branched‐chain ketoacid dehydrogenase and components of the ATP‐ubiquitin‐proteasome dependent proteolytic pathway. the response also involves increased transcription of genes encoding these enzymes. Understanding regulation of these pathways could improve therapy of uraemia and other catabolic illnesses because the same pathways are activated in cancer, sepsis, burns, starvation and muscle dene