Skeletal muscle ribonuclease activities in chronically ethanol-treated rats

Alcoholic myopathy occurs in up to two thirds of alcohol misusers and is characterized by selective atrophy of type II (anaerobic, fast-twitch) fibers; type I (aerobic, slow twitch) fibers are relatively unaffected. Both clinical and animal studies have indicated that skeletal muscle RNA content is reduced in response to ethanol exposure, and contributes to impaired protein synthesis. We hypothesized that the reduction in muscle RNA may be due to raised ribonuclease (RNase) activities that enhance RNA catabolism. To test this hypothesis, we measured the total tissue and plasma RNase activities as well as the activities of general (RNase A) and specific or "restriction" RNases (T1L, T2L) in ethanol-treated rats. Chronically treated rats were fed a nutritionally complete liquid diet with 35% of calories as ethanol. Weight-matched controls were pair-fed with isocaloric glucose. Rats were killed at time-points up to 6 weeks. For comparative purposes, the effect of acute (24 hr) starvation was also analyzed in a second group of rats relative to a group of control rats allowed free access to food and water over 24 hr. Results showed that the type II fiber-predominant plantaris muscle exhibited a significant increase in total RNase, RNase A and RNase T1L activities (increases ranged from +59% to +196%; P-values between 0.025 and 0.01) concomitant with large falls in RNA and protein content. In contrast, none of the RNase activities measured in the type I fiber-predominant soleus muscles were significantly affected; compositional changes were also smaller in the soleus. This effect was independent of reduced nutrition. In conclusion, the raised total RNase, RNase A and RNase T1L activities may contribute to the type II fiber-specific reduction in total RNA in chronically ethanol-treated rats. In turn, this may contribute to the alterations in cellular protein metabolism seen under these treatments.