Cellular and molecular signatures of alcohol-induced myopathy in women

Am J Physiol Endocrinol Metab. 2019 May 1;316(5):E967-E976. doi: 10.1152/ajpendo.00513.2018. Epub 2019 Mar 26.

Abstract

Alcoholic myopathy is characterized by the reduction in cross-sectional area (CSA) of muscle fibers and impaired anabolic signaling. The goal of the current study was to investigate the causes and compare the changes in CSA and fiber type composition with the modifications of anabolic and catabolic signaling pathways at the early stages of chronic alcohol consumption in women. Skeletal muscle samples from 5 female patients with alcohol abuse (AL; 43 ± 5 yr old; alcohol abuse duration 5,6 ± 0,6 yr) were compared with the muscle from the control group of 8 healthy women (C; 35 ± 4 yr old). The average daily dose of alcohol consumption was 110 ± 10 ml of pure ethanol. In women patients, a significant decrease in CSA of type I and II muscle fibers, titin and nebulin content, plasma IGF-1 level and total IRS-1, p-Akt and p-4E-BP1 in vastus lateralis was found in comparison with the control group. The p-AMPK level was found to be increased versus the control group. In women patients with chronic alcoholic myopathy 1) both fast and slow muscle fibers are subjected to atrophy; 2) impairments in IGF-I-dependent signaling and pathways controlling translation initiation (AMPK/mTOR/4E-BP1), but not translation elongation, are observed; 3) the level of calpain-1 and ubiquitinated proteins increases, unlike E3 ligases content.

Keywords: ethanol; insulin-like growth factor-1, insulin receptor substrate-1; p70S6K1; p90RSK; ubiquitinated proteins.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adaptor Proteins, Signal Transducing / metabolism
  • Adenylate Kinase / metabolism
  • Adult
  • Alcohol-Induced Disorders / metabolism*
  • Alcohol-Induced Disorders / pathology
  • Alcoholism / metabolism*
  • Case-Control Studies
  • Cell Cycle Proteins / metabolism
  • Connectin / metabolism
  • Female
  • Humans
  • Insulin Receptor Substrate Proteins / metabolism
  • Insulin-Like Growth Factor I / metabolism
  • Middle Aged
  • Muscle Fibers, Fast-Twitch / metabolism*
  • Muscle Fibers, Fast-Twitch / pathology
  • Muscle Fibers, Slow-Twitch / metabolism*
  • Muscle Fibers, Slow-Twitch / pathology
  • Muscle Proteins / metabolism
  • Muscle, Skeletal / metabolism
  • Muscle, Skeletal / pathology
  • Muscular Diseases / metabolism*
  • Muscular Diseases / pathology
  • Organ Size
  • Phosphoproteins
  • Proto-Oncogene Proteins c-akt / metabolism
  • Quadriceps Muscle / metabolism*
  • Quadriceps Muscle / pathology
  • Signal Transduction
  • TOR Serine-Threonine Kinases / metabolism

Substances

  • Adaptor Proteins, Signal Transducing
  • Cell Cycle Proteins
  • Connectin
  • EIF4EBP1 protein, human
  • IRS1 protein, human
  • Insulin Receptor Substrate Proteins
  • Muscle Proteins
  • Phosphoproteins
  • nebulin
  • Insulin-Like Growth Factor I
  • MTOR protein, human
  • Proto-Oncogene Proteins c-akt
  • TOR Serine-Threonine Kinases
  • Adenylate Kinase