AJP - Cell Physiology, Vol 262, Issue 6 C1513-C1519, Copyright © 1992 by American Physiological Society
Sepsis-induced changes in protein synthesis: differential effects on fast- and slow-twitch muscles
T. C. Vary and S. R. Kimball
Department of Cellular and Molecular Physiology, Pennsylvania State University College of Medicine, Hershey 17033.
Sepsis is associated with severe muscle wasting. Mechanisms responsible for
sepsis-induced alterations in muscle protein metabolism were investigated
in vivo and compared with changes induced by nonseptic inflammation. The
rate of protein synthesis in mixed hindlimb muscles was not altered in
inflammation but was inhibited 50% in sepsis. This inhibition did not
result from a decreased RNA content. Instead, the translational efficiency
was significantly reduced by 50% in skeletal muscle of septic animals
compared with control. The effect of sepsis to lower the rate of protein
synthesis was further examined using individual muscles containing
different fiber types. Both the protein concentration and protein synthetic
rate in fast-twitch muscles were reduced by sepsis, whereas neither of
these parameters was affected in slow-twitch muscles or heart. The
decreased translational efficiency did not result from a change in the rate
of peptide-chain elongation. Instead, the sepsis-induced inhibition of
protein synthesis resulted from a restraint in peptide-chain initiation
because sepsis caused a 1.6-fold increase in free ribosomal subunits.
Overall, sepsis, but not inflammation, caused an inhibition of protein
synthesis primarily in muscles composed of fast-twitch fibers. The
mechanism involved in the reduced rates of protein synthesis in muscles
resulted from an inhibition of peptide-chain initiation, with no change in
peptide-chain elongation.
