Muscle protein synthesis: regulation of a translational inhibitor

Abstract

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.

Diabetes-induced alterations in the translational activity of specific messenger ribonucleic acids isolated from rat hearts.

“…Total protein synthesis is affected by insulin in the heart (Pain et al, 1974;Williams et al, 1980), as well as in noncardiac tissues (DePhilip et al, 1980;Hill et al, 1981;Buse et al, 1984). By using RNA translation in cell-free systems or RNA hybridization to specific deoxyribonucleic acid (DNA) probes, it has been possible to demonstrate that this regulation occurs at a pretranslational level.…”

Effects of Dietary Supplementation with Branched-chain Amino Acids (BCAAs) during Nursing on Plasma BCAA Levels and Subsequent Growth in Cattle

“…In immature swine, an excess of dietary BCAAs induces different growth rates in different muscle types (Richmond, 1982), and the levels of essential amino acids in the liver are responsive to dietary protein intake (Bergen and Potter, 1975). In rats, leucine supplementation increases protein synthesis in the diaphragm (Buse and Weigand, 1977), perfused hind limbs (Buse et al, 1984), and isolated skeletal muscles (Hong and Layman, 1984). As results showing in Figure 2, the aspect of absorbance ration of amino acids varies from 1 to 4 weeks age.…”

Animal Growth Regulation

“…1982) and branched-chain keto acid dehydrogenase complexes. It remains to be proven whether the control of EIFra phosphorylation involves primarily the reduction of the activity of a protein kinase, as suggested by the results of Buse et al .. (1984), or the activation of a counteracting phosphatase (Foulkes et al, 1980;Ernst et al .. 1982;Macauley and Jarett, 1985). At the present time, there is little direct evidence for a role for EIF2 phosphorylation in cells other than the reticulocyte (but see Towle et al .. 1984), although it is tempting to speculate that precisely the same "factor" is involved in the coordinate stimulation of muscle protein synthesis, fat deposition, glucose oxidtion, and storage induced by insulin (Table VI).…”

“…One end result of these events appears to be the release into the intracellular phase of a number of "mediators." These may include both peptides (Lamer et al, 1982;Buse et al, 1984) and glycoinositides (Saltiel and Cuatrecasas, 1986). These mediators then presumably act by altering the activities of the cytoplasmic, mitochondrial, and nuclear protein kinases and phosphatases.…”