title: Muscle wasting and the temporal gene expression pattern in a novel rat intensive care unit model.
abstract: BACKGROUND
  Acute quadriplegic myopathy (AQM) or critical illness myopathy (CIM) is frequently observed in intensive care unit (ICU) patients. To elucidate duration-dependent effects of the ICU intervention on molecular and functional networks that control the muscle wasting and weakness associated with AQM, a gene expression profile was analyzed at time points varying from 6 hours to 14 days in a unique experimental rat model mimicking ICU conditions, i.e., post-synaptically paralyzed, mechanically ventilated and extensively monitored animals.
  
  
  RESULTS
  During the observation period, 1583 genes were significantly up- or down-regulated by factors of two or greater. A significant temporal gene expression pattern was constructed at short (6 h-4 days), intermediate (5-8 days) and long (9-14 days) durations. A striking early and maintained up-regulation (6 h-14d) of muscle atrogenes (muscle ring-finger 1/tripartite motif-containing 63 and F-box protein 32/atrogin-1) was observed, followed by an up-regulation of the proteolytic systems at intermediate and long durations (5-14d). Oxidative stress response genes and genes that take part in amino acid catabolism, cell cycle arrest, apoptosis, muscle development, and protein synthesis together with myogenic factors were significantly up-regulated from 5 to 14 days. At 9-14 d, genes involved in immune response and the caspase cascade were up-regulated. At 5-14d, genes related to contractile (myosin heavy chain and myosin binding protein C), regulatory (troponin, tropomyosin), developmental, caveolin-3, extracellular matrix, glycolysis/gluconeogenesis, cytoskeleton/sarcomere regulation and mitochondrial proteins were down-regulated. An activation of genes related to muscle growth and new muscle fiber formation (increase of myogenic factors and JunB and down-regulation of myostatin) and up-regulation of genes that code protein synthesis and translation factors were found from 5 to 14 days.
  
  
  CONCLUSIONS
  Novel temporal patterns of gene expression have been uncovered, suggesting a unique, coordinated and highly complex mechanism underlying the muscle wasting associated with AQM in ICU patients and providing new target genes and avenues for intervention studies.
authors.affiliation: Department of Clinical Neurophysiology, Uppsala University, Uppsala, Sweden.
authors.forename: Monica
authors.initials: M
authors.lastname: Llano-Diez
authors.forename: Ann-Marie
authors.initials: AM
authors.lastname: Gustafson
authors.forename: Carl
authors.initials: C
authors.lastname: Olsson
authors.forename: Hanna
authors.initials: H
authors.lastname: Goransson
authors.forename: Lars
authors.initials: L
authors.lastname: Larsson
mesh_terms: D000818:Animals; D020869:Gene Expression Profiling; D007362:Intensive Care Units; D008954:Models, Biological; D009124:Muscle Proteins / Q000235:genetics; D009133:Muscular Atrophy / Q000235:genetics*; D018384:Oxidative Stress; D059748:Proteolysis; D051381:Rats
chemical_list: D009124:Muscle Proteins