Doctoral Dissertations

Date of Award

12-1997

Degree Type

Dissertation

Degree Name

Doctor of Philosophy

Major

Life Sciences

Major Professor

Michael D. Karlstad

Committee Members

Roger C. Carroll, Karla J. Matteson

Abstract

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.

Download
Files over 3MB may be slow to open. For best results, right-click and select "save as..."

Share

COinS