INDUCTION OF PROLONGED TOLERANCE TO THIRD-PARTY SKIN GRAFTS FOLLOWING FULLY ALLOGENEIC BONE MARROW TRANSPLANTATION IN MICE

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Abstract
Degradative cytosolic proteolysis contributes to cell injury following ATP depletion. Although ATP depletion is a salient feature of ischemie liver storage for transplantation, information regarding cytosolic protease activity during liver storage is lacking. Thus our aim was to measure liver cytosolic protease activity following ischemie storage. A progressive increase in total cytosolic protease activity was observed over time at both 37°C and 47deg;C, but the increase was greater at 37deg;C. Total cellular proteolysis was also temperature-dependent during anoxia (37deg;C 7gt; 4deg;C), demonstrating a physiologic correlation between cellular proteolysis and measurements of cytosolic protease activity. The stimulation of total cytosolic protease activity was due to an increase in métallo- and aspartate protease activity. Of particular interest, glutathione (GSH) inhibited both metalloprotease and aspartate protease activity from cytosol of stored livers. Glycine, the carboxyl-terminal amino acid of GSH, also inhibited both metalloprotease and aspartate protease activity. In addition to being an antioxidant, GSH may exert its protective effects during organ preservation by inhibiting cytosolic proteases—perhaps via its glycine moiety. These experiments support the hypothesis that degradative proteolysis contributes to liver injury during organ preservation.

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