Muscle protein metabolism during sepsis

Introduction One of the most pronounced metabolic changes after injury, sepsis and other critical illness is increased urinary excretion of nitrogen, resulting in negative nitrogen balance. There is evidence that skeletal muscle is the major source of nitrogen in these conditions. Muscle catabolism during sepsis is mainly caused by increased protein degradation, in particular myofibrillar protein breakdown, although reduced protein synthesis and inhibited amino acid uptake contribute to the catabolic response [ l ] (Figure 1). One consequence of muscle breakdown is release of amino acids with redistribution from the periphery to central organs and tissues, such as liver and intestine [2]. A large amount of amino acids released from skeletal muscle during catabolic conditions is taken up by the liver for gluconeogenesis and acute phase protein synthesis. Glutamine released from catabolic muscle is taken up by cells of the immune system [3] and by intestinal epithelial cells [4] and is an important energy source in these cell types. Thus, muscle catabolism is part of an integrated response to sepsis and may be beneficial to the organism, at least during the early phase of sepsis, providing essential tissues with increased amounts of amino acids. If allowed to continue uncontrolled, however, muscle breakdown will result in muscle wasting, fatigue and delayed recovery. The term ‘autocannibalism’ has been used to illustrate the serious consequences of muscle proteolysis during severe and protracted sepsis [5]. Considering the important clinical implications of muscle breakdown, it is not surprising that much research has been performed to define mediators and mechanisms of muscle proteolysis during sepsis. In this report, recent knowledge about the regulation of muscle protein breakdown during sepsis is reviewed together with mechanisms and molecular regulation of intracellular protein degradation.