FRACTIONAL SYNTHESIS OF INDIVIDUAL HEPATIC PROTEINS UNDER SEPTIC SHOCK

Abstract

Objective: Septic shock-associated oxidative stress may impair mitochondrial functioning and energy metabolism, radical side products have to be detoxified, and defence proteins have to be synthesized. The hepatic adaptation to these challenges should be reflected in the pattern of synthesis of individual proteins. Methods: 5 mice with cecal ligation induced peritonitis were compared with 6 sham operated or untreated controls. 13C6-glucose was given by constant infusion, the 13C-label was incorporated into proteins during their synthesis. Thus, the mass distribution of peptide fragments was altered, which was quantified by Maldi-TOF mass spectrometry after separation of hepatic proteins by large Gel 2D electro-phoresis. Results: Compared to sham animals the overall fractional synthesis of proteins is reduced under peritonitis, with the largest reduction for pheromone carrying proteins (mouse urinary proteins). The synthesis of constituent heat shock proteins is slightly reduced, enzymes of glucose metabolism as well as SOD-1 appear unaffected, and the repair protein "protein disulfide isomerase" slightly increased. Albumin increases from untreated controls to sham and sepsis. Conclusions: The overall hepatic capacity for protein synthesis appears to be reduced in septic shock, and the remaining capacity is focused on proteins necessary to overcome sepsis. Individual changes should be interpreted in view of the overall reduction, and, hence, the stimulated albumin synthesis deserves further investigation. Supported by EU-Project LSHG-CT-2005-512044.