Catabolic response to stress and injury: implications for regulation.
Muscle catabolism is an important component of the metabolic response to stress and injury, including sepsis and burn injury. Muscle wasting and weakness in catabolic patients may adversely affect the outcome in these patients owing to delayed ambulation and involvement of respiratory muscles. An understanding of the regulation of muscle protein breakdown during sepsis and following injury therefore is of great importance from a clinical standpoint and is essential for the development of new therapeutic modalities to prevent protein loss from muscle tissue. Studies in experimental animals and in patients have provided evidence that the myofibrillar proteins actin and myosin are particularly sensitive to the effects of sepsis and injury. (Glucocorticoids, interleukin-1, and tumor necrosis factor participate in the regulation of muscle protein breakdown. Most muscle proteins are degraded by the ubiquitin-proteasome-dependent proteolytic pathway. Because the proteasome does not degrade intact myofibrils, a calcium-dependent Z-band disintegration and release of myofilaments from the myofibrils may be an important initial step of muscle breakdown during sepsis and other catabolic conditions. Continued studies to define mechanisms of the catabolic response to stress and injury are important for improving the metabolic care of patients with muscle catabolism.
Hasselgren
P O
PO
Department of Surgery, University of Cincinnati College of Medicine, Ohio 45267-0588, USA.
D000818:Animals; D016207:Cytokines / Q000378:metabolism; D005938:Glucocorticoids / Q000378:metabolism; D006801:Humans; D007328:Insulin / Q000378:metabolism; D007334:Insulin-Like Growth Factor I / Q000378:metabolism; D009124:Muscle Proteins / Q000378:metabolism*; D009210:Myofibrils / Q000378:metabolism; D018805:Sepsis / Q000378:metabolism*; D014452:Ubiquitins / Q000378:metabolism; D014947:Wounds and Injuries / Q000378:metabolism*
D016207:Cytokines; D005938:Glucocorticoids; D007328:Insulin; D009124:Muscle Proteins; D014452:Ubiquitins; D007334:Insulin-Like Growth Factor I