Altered expression of eukaryotic initiation factor 2B in skeletal muscle during sepsis

Sepsis causes an inhibition of protein synthesis in skeletal muscles composed of fast-twitch fibers, in part, as a result of a decreased activity of the eukaryotic initiation factor 2B (eIF-2B). In the present study, we investigated the expression of two subunits of eIF-2B, i.e., the β- and ε- subunits during sepsis. The expression of both βand ε-subunits of eIF-2B in gastrocnemius was decreased ~50% from control values during the first 5 days after induction of sepsis. The decreased expression of eIF-2Bε during sepsis correlated with similar reductions in eIF-2Bε mRNA. Restoration of protein synthesis (10 days postsurgery) was associated with a return of eIF-2Bε expression to values observed in control rats. Expression of eIF-2Bε was not altered in heart during sepsis or in gastrocnemius from nonseptic abscess animals. Amrinone, which ameliorated the inhibition of protein synthesis during sepsis, also prevented the fall in eIF-2Bε protein after 5 days of infection. The data provide evidence that expression of eIF-2Bε is markedly influenced in gastrocnemius during the course of the septic episode and support the concept that this change is a mechanism responsible for the inhibition of protein synthesis observed under this condition.