Protein and mRNA levels of the myosin heavy chain isoforms I beta, IIa, IIx and IIb in Type I and Type II fibre-predominant rat skeletal muscles in response to chronic alcohol feeding

Alcoholic myopathy occurs in between one and two-thirds of all alcohol misu sers and is thus one of the most prevalent muscle disorders (2000 cases per 100,000 population). It is characterised by myalgia, muscle weakness and l oss of lean tissue mass. Histological features include a reduction in the d iameter of Type II muscle fibres, particularly the IIb fibre subset. In con trast, Type I fibres are relatively protected. It is possible that the myop athy is due to perturbations in myosin protein and mRNA expression. To test this hypothesis, we fed rats a liquid diet containing 35% of calories as e thanol. Control rats were pair-fed identical amounts of the same diet in wh ich ethanol was replaced by isocaloric glucose. At the end of 6 weeks, tota l myofibrillary proteins and myosin heavy chain (MyoHC) I beta, IIa, IIx an d IIb protein and mRNA were analysed in the plantaris (Type II fibre-predom inant) and soleus (Type I fibre-predominant) muscles. The data showed that there were significant reductions in the total myofibrillary protein conten t in the plantaris of ethanol fed rats compared to pair-fed controls (P < 0 .05). These changes in the plantaris were accompanied by reductions in tota l myosin (P < 0.025), as a consequence of specific reductions in the I beta , (P < 0.01), IIx (P < 0.05) and IIb (P < 0.05) protein isoforms. The mRNA levels of I beta were significantly reduced in the plantaris (P < 0.05). Ho wever, mRNA levels of IIa, IIx and IIb in the plantaris were not significan tly affected by alcohol feeding. Other changes in the plantaris included si gnificant reductions in desmin (P < 0.01), actin (P < 0.025), and troponin- I (P < 0.05) compared to pair-fed controls. In the soleus, the only signifi cant changes related to a fall in I beta mRNA levels and a decline in tropo nin-C content. We conclude that in the rat, alcoholic myopathy is a feature of Type II fibre rich muscles and is accompanied by multiple protein chang es. The decline in specific myosin protein levels, such as IIx and IIb in t he absence of corresponding reductions in their mRNAs, is probably due to a ltered proteolysis or more likely reductions in translational efficiencies, rather than changes in transcription.