Russian Academy of Sciences, Moscow, Russia
Chronic alcoholic myopathy is one of most numerous and profound manifestations of chronic alcohol intoxication. This disease is characterized by the pronounced atrophy of the locomotor muscles, which involves predominantly those fibers expressing myosin isoforms of the II “fast” type. At the same time patients at the early stages of the disease development not always demonstrate signs of fiber atrophy. In early experiments with alcohol-fed rats it was shown the impairment of the anabolic intracellular signaling pathways and decrease in protein synthesis rate. However the alterations of the signaling pathways in muscles of patients with alcoholic myopathy are not studied yet. In our lab we were the first to analyze the signaling pathways involved in the pathogenesis of alcoholic myopathy with different fiber atrophy levels. In biopsy samples of m. vastus lateralis (even at the early stages of the disease) we found dramatic drop of the phosphorylation levels of S6 ribosomal kinases and increase in phosphorylation of the eukaryotic elongation factor-2, which facilitate the decrease of the protein synthesis levels. At the early stages we observed also the significant increase of mRNA of E3 ubiquitin ligases. However the ubiquitinylation level was not altered in patients as compared to the control subjects. This phenomenon could be associated with the increased expression of the heat-shock proteins, known for their protective action. Thus in patients with alcoholic myopathy we revealed the impairment of the anabolic as well as catabolic signaling pathways in skeletal muscle. The study was performed in collaboration with the Neurological Clinic of the Sechenov First Moscow State Medical University and funded by the Program of the RAS Presidium “Basic Sciences for Medicine”.