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 beta- and epsilon-subunits during
sepsis. The expression of both beta- and epsilon-subunits of
eIF-2B in gastrocnemius was decreased approximately 50% from control values during the first 5 days after induction of
sepsis. The decreased expression of
eIF-2B epsilon during
sepsis correlated with similar reductions in
eIF-2B epsilon
mRNA. Restoration of
protein synthesis (10 days postsurgery) was associated with a return of
eIF-2B epsilon expression to values observed in control rats. Expression of
eIF-2B epsilon 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-2B epsilon
protein after 5 days of
infection. The data provide evidence that expression of
eIF-2B epsilon 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.