INHIBITION OF PROTEIN-SYNTHESIS BY ACID IN L6 SKELETAL-MUSCLE CELLS -ANALOGIES WITH THE ACUTE STARVATION RESPONSE

Impaired protein synthesis (PS) occurs in skeletal muscle during acute starvation. Even though it is well established that uraemic metabolic acidosis (MA) stimulates protein degradation (PD) and is a major cont ributor to skeletal muscle wasting in chronic renal failure, the accom panying effects of MA on PS are much less clear. Previous work has sho wn that, in cultured L6 skeletal muscle cells, PD and leucine oxidatio n are stimulated by acid. The aim of the present study was to determin e whether acid (like acute starvation) can also inhibit PS. PS (C-14-p henylalanine incorporation) was measured in L6 cells in MEM + 2% serum at acid pH (7.1) or control pH (7.5). After 24 h, acid inhibited PS ( 7.7 +/- 0.2 vs. 8.9 +/- 0.1 nmol Phe/4 h/35-mm culture well in control s, p = 0.01) and this was maintained at 72 h. In vitro this could aris e because acid only inhibits the rapid PS occurring in dividing cells. However, when division was abolished with 10(-5) mol/l cytosine arabi noside, PS inhibition by acid still occurred(6.9 +/- 0.1 vs. 8.3 +/- 0 .2 at control pH, p < 0.05). Acid also had no effect on the specific r adioactivity of cellular phenylalanine, suggesting that the impaired P S was not a consequence of inadequate labelling of this pool. Elevated PD and impaired PS together led to loss of 7% of the total protein in only 28 h (-21 +/- 3 mu g/well, p = 0.004). This combination of impai red PS with increased PD and increased leucine oxidation in response t o acid resembles the response of skeletal muscle to acute starvation. These superficial similarities between the starvation state and MA sug gest that fundamental metabolic signals may occur which are common to both states.