The role of platelet-activating factor in alterations of amino acid transport and protein metabolism during shock

Platelet-activating factor (PAF), a biologically active phospholipid, has been implicated as an important mediator of endotoxin shock and sepsis. An attenuation of amino acid transport and acceleration of net protein loss from skeletal muscle are major characteristics of the protein catabolic response to septic shock. This dissertation is composed of two parts and is devoted to understanding the role of PAF as a potential mediator of protein catabolism during shock and sepsis. The first part demonstrates that a) PAF attenuates system A amino acid transport in skeletal muscle during endotoxic shock by producing conditions and/or factors in plasma that might be similar to those existing during endotoxemia and, b) the direct attenuation of amino acid transport depends upon previous exposure of skeletal muscle to those conditions or factors generated by PAF in vivo. The second part demonstrates that PAF induces net protein catabolism as a result of a) elevated leucine oxidation at the expense of protein synthesis, b) attenuated rate of fractional protein synthesis in skeletal muscle, c) reduced efficiency of muscle protein synthesis, and d) decreased myosin relative abundance in skeletal muscle. PAF attenuates amino acid uptake and reduces protein synthesis in skeletal muscle and thus is a potential mediator of protein catabolism during shock. The first part of this dissertation was previously published (SHOCK 2(1):53-59, 1994) and the second part is in preparation for publication.