STUDIES ON THE TIME-COURSE OF ETHANOLS ACUTE EFFECTS ON SKELETAL-MUSCLE PROTEIN-SYNTHESIS - COMPARISON WITH ACUTE CHANGES IN PROTEOLYTIC ACTIVITY

A study of the effects of ethanol on skeletal muscle protein synthesis and protease activities was carried out in young male Wistar rats (15 0 g) for up to 24 hr after a single intraperitoneal dose of 75 mmol of ethanol/kg of body weight. At 20 min, the mean blood ethanol levels w ere 448 mg/dl. This level dropped steadily to zero through the followi ng 24 hr. Compared with pair-fed controls, significant reductions in t otal protein, RNA, and DNA contents were seen only after 24 hr in all skeletal muscles studied: changes were more marked in the muscles cont aining large proportions of type II fibers. In plantaris muscle, the f ractional rate of protein synthesis (k(s), %/day) did not fall 20 min after dosage but was reduced after 1 hr by 23% (p < 0.001), and by 63% after 24 hr, compared with control saline-injected rats (p < 0.001). This effect was independent of dietary intake because, compared with t he pair-fed group, the 24-hr ethanol-treated rats still showed a 52% d ecrease in fractional rates of protein synthesis (p < 0.001). Smaller reductions in k(s) were seen in solseus muscles in response to ethanol at 24 hr (-39%, p < 0.001). The activities of a variety of lysosomal and nonlysosomal proteases in plantaris muscle of 24-hr treated rats w ere not significantly affected by ethanol. Only alanyl- and tripeptidy l-aminopeptidase activities were reduced significantly (26%, p < 0.05 and 39%, p < 0.01, respectively). These results suggest that the muscl e compositional changes seen over acute periods of ethanol toxicity ar e predominantly associated with impaired synthesis of protein and that the contribution of cellular proteolytic systems may be minimal. The effects of ethanol on skeletal muscle protein metabolism are greater i n muscles containing a predominance of type II fibers than in those co ntaining mainly type I fibers. Ethanol's effects on muscle may be infl uenced by hormonal changes after 24 hr, because protein synthesis is s till compromised and free plasma T3 and corticosterone are altered at this time-point.