Total contractile protein contents and gene expression in skeletal muscle in response to chronic ethanol consumption in the rat.

An investigation was carried out to determine changes in the contents of skeletal muscle myofibrillary proteins (i.e., the contractile fraction composed principally of actin and myosin) and gene expression in skeletal muscle in response to ethanol feeding. Male Wistar rats were fed a nutritionally complete liquid diet, which contained 35% of total calories as ethanol. Controls were pair-fed isocaloric amounts of the same diet, in which ethanol was replaced by isocaloric glucose. Total mixed and contractile protein contents of the gastrocnemius in ethanol-fed rats were rapidly reduced by ethanol feeding: a response was discernible as early as 1 week after the commencement of the ethanol feeding regimen (approx. -10%, p < 0.025 and p = 0.05 for mixed and myofibrillary proteins, respectively). At 2, 4, and 6 weeks, mixed and myofibrillary protein contents were further reduced in alcohol-fed rats, by between 12% and 22%, compared to pair-fed controls. Similar changes occurred in the soluble (i.e., sarcoplasmic) protein fractions of skeletal muscle. At 2 weeks the composition of total messenger RNA and individual messenger RNA species was measured. Total messenger RNA content per muscle was reduced by 35% (p < 0.05). Messenger RNA levels for alpha-actin, beta-myosin heavy chain, and carbonic anhydrase III were not significantly altered. In conclusion, skeletal muscle protein contents are rapidly reduced by ethanol feeding, compared to pair-fed controls, though mRNA species encoding specific isoforms of myosin and actin are not affected. It is possible that chronic ethanol feeding may significantly alter the stability of mRNAs encoding other contractile proteins, or alternatively, defects in translation may predominate.