AJP - Endocrinology and Metabolism, Vol 246, Issue 6 510-E515, Copyright © 1984 by American Physiological Society
Muscle protein synthesis: regulation of a translational inhibitor
M. G. Buse, I. R. Cheema, M. Owens, B. E. Ledford and R. A. Galbraith
Insulin and branched-chain amino acids are known to stimulate protein
synthesis in skeletal muscle. Extracts prepared from rat diaphragms after
incubation in balanced salt solution and glucose alone yielded heat- and
acid-stable, TCA-precipitable, nondialyzable factor(s) that inhibit protein
synthesis when added to rabbit reticulocyte lysates. Polyribosomal profiles
of inhibited lysates were consistent with a defect in peptide-chain
initiation. Addition of insulin and amino acids to the diaphragm incubation
media partially removed the inhibition seen with the muscle extract and was
accompanied by an increase in polysomes and decreased subunits. Similarly,
extracts prepared from rat hindlimb muscle 48 h after induction of diabetes
were much more inhibitory in rabbit reticulocyte lysates than extracts from
control rats. Polyribosomal profiles were consistent with defective
peptide-chain initiation. Trypsin treatment before assay abolished the
inhibitory activity of muscle extracts from diabetic rats. Because
translation-inhibiting peptide(s) appear to be under metabolic and/or
hormonal control, their possible role in muscle protein homeostasis
warrants further study.
