Regulation of Eukaryotic Initiation Factor-2 Expression During Sepsis

Protein synthesis is stimulated at the level of peptide chain initiation in livers from rats with a sterile or septic abscess. In contrast, peptide chain initiation is inhibited in fast-twitch skeletal muscles from septic rats. We investigated the possible mechanisms responsible for these differential changes in peptide chain initiation between liver and skeletal muscle during sepsis by measuring the cellular content of eukaryotic initiation factor-2 (eIF-2), the extent of phosphorylation of the alpha-subunit of eIF-2, and the activity of eIF-2B. In skeletal muscle, neither the eIF-2 content nor the extent of phosphorylation of eIF-2 alpha was altered during sepsis. However, a significant decrease (P < 0.001) in eIF-2B activity was observed in fast-twitch muscles. In liver, neither the extent of phosphorylation of eIF-2 alpha nor the activity of eIF-2B was different in rats with a sterile or septic abscess compared with control. However, the amount of eIF-2 in liver was increased in both sterile inflammation and sepsis. The relative abundance of eIF-2 alpha mRNA was not increased in either condition compared with control. Analysis of the distribution of eIF-2 alpha mRNA from control rats revealed that only approximately 40% of the message was associated with polysomes. Sterile inflammation or sepsis caused a 50% increase in the proportion of eIF-2 alpha mRNA associated with the polysomes compared with control.(ABSTRACT TRUNCATED AT 250 WORDS)