Studies on the time-course of ethanol's acute effects on skeletal muscle protein synthesis: comparison with acute changes in proteolytic activity

Abstract

A study of the effects of ethanol on skeletal muscle protein synthesis and protease activities was carried out in young male Wistar rats (150 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 were 448 mg/dl. This level dropped steadily to zero through the following 24 hr. Compared with pair-fed controls, significant reductions in total protein, RNA, and DNA contents were seen only after 24 hr in all skeletal muscles studied: changes were more marked in the muscles containing large proportions of type II fibers. In plantaris muscle, the fractional rate of protein synthesis (ks, %/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 the pair-fed group, the 24-hr ethanol-treated rats still showed a 52% decrease in fractional rates of protein synthesis (p < 0.001). Smaller reductions in ks were seen in soleus 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 were not significantly affected by ethanol. Only alanyl- and tripeptidyl-aminopeptidase activities were reduced significantly (26%, p < 0.05 and 39%, p < 0.01, respectively). These results suggest that the muscle compositional changes seen over acute periods of ethanol toxicity are 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 in muscles containing a predominance of type II fibers than in those containing mainly type I fibers. Ethanol's effects on muscle may be influenced by hormonal changes after 24 hr, because protein synthesis is still compromised and free plasma T3 and corticosterone are altered at this time-point.