Effect of Chronic Alcohol Abuse on Anabolic and Catabolic Signaling Pathways in Human Skeletal Muscle.

BACKGROUND: Animal studies showed that alcoholic myopathy is characterized by the reduction in myofiber cross-sectional area (CSA) and by impaired anabolic signaling. The goal of this study was to compare changes in CSA and fiber type composition with modifications in anabolic and catabolic signaling pathways at the early stages of alcohol misuse in humans. METHODS: Skeletal muscle samples from 7 male patients with chronic alcohol abuse (AL; 47.7 ± 2.0 years old; alcohol misuse duration 7.7 ± 0.6 years) were compared with muscle from a control group of 7 healthy men (C; 39.7 ± 5.0 years old). Biopsies from vastus lateralis muscles were taken and analyzed for the changes in fiber type composition, fiber CSA, and for the alterations in anabolic and catabolic signaling pathways. RESULTS: AL patients did not have detectable clinical myopathy symptoms or muscle fiber atrophy, but the relative proportion of fast fibers was increased. There was a significant decrease in IGF-1 in plasma and IRS-1 protein content in muscle of AL group. Levels of total and phosphorylated p70S6K1, GSK3ß, and p90RSK1 were not different between AL and C groups. Muscle of AL patients had increased mRNA expression of HSP70 and HSP90. A marker of anabolic pathway p-4E-BP1 was decreased, while catabolic markers (MuRF-1, MAFbx, ubiquitinated proteins) were increased in AL patients when compared with C group. CONCLUSIONS: At the early stages of alcohol misuse in humans, changes in the regulation of anabolic and catabolic signaling pathways precede the development of skeletal muscle atrophy and manifestation of clinical symptoms of alcoholic myopathy.

Effect of short-term gravitational unloading on rat and mongolian gerbil muscles.

Gravitational unloading leads to destructive changes in the structure and function of muscle fibers. However, the role of the EMG activity level is still unclear. We measured changes caused by one- and three-day hypogravity in the following muscles: Soleus (Sol), Tibialis anterior (TA) and Gastrocnemius c.m. (MG). We used Wistar rats and Mongolian gerbils. The following parameters were assessed: the specific force of contraction of isolated fibers by tensometry, the transverse stiffness of the contractile apparatus by atomic force microscopy, and the calcium content by Fluo-4. We detected the accumulation of calcium ions in all muscles even after one-day unloading. In Sol this effect was more significant than in other muscles. After one-day of hypogravity we detected an increase in the specific force in all muscle types and species. Meanwhile, the transverse stiffness of the contractile apparatus, M-band and Z-disc increased only in fast muscles but not in Sol. After three-days of unloading, the specific force in Sol decreased, and the transverse stiffness of the contractile apparatus behaved in the same way as the force. The specific tension of fast muscle fibers decreased significantly in comparison with one-day unloading. In addition, the transverse stiffness of some areas of MG had a tendency to decrease in comparison to "one-day" unloading, although there was no such a tendency in the fibers of TA. In Mongolian gerbils the tendencies were the same as in the rats, but showed less dramatic changes. The reduction in the magnitude of changes in the Sol-MG-TA series correlates with EMG activity.