CHRONIC-ALCOHOLIC MYOPATHY - TRANSCRIPTION AND TRANSLATIONAL ALTERATIONS

Alcoholic myopathy is characterized by selective atrophy of type II fibers and affected subjects lose up to 20% of the entire musculature. Between one and two-thirds of all alcohol abusers are affected. In acute studies, defective rates of translation occur and type II fiber-predominant muscles are more adversely affected than type I fiber-predominant muscles. Furthermore, acetaldehyde is also a potent modulator of translation, and contractile and noncontractile proteins are affected equally. In chronic ethanol feeding there is rapid and sustained loss of ribosomal RNA. Recent attention has focused on the observation that total messenger RNA (mRNA) falls after ethanol consumption, but mRNA for specific myofibrillary contractile proteins are unaffected, implicating a role for translational modifications in the initial stages of the myopathy. Clinical studies have also shown that chronic alcohol abusers have defective rates of muscle protein synthesis and whole-body protein metabolism. The modulations in transcription and translation are not mediated by availability of amino acids, the effects of endocrine dysfunction (cortisol and growth hormone), liver impairment, or malnutrition. Free radicals, however, may be contributory mediators. Receptor-mediated events and the putative roles of growth factors are generally unexplored, though a distinguishing feature of acute ethanol administration is a reduction in circulating IGF-I. Thus, ethanol may act directly on muscle, although other concordant processes may coexist.