title: Ubiquitin ligases MuRF1 and MAFbx in human skeletal muscle atrophy.
abstract: BACKGROUND
  Several pathological conditions can induce skeletal muscle atrophy and seem to share common enzyme pathways. In catabolic states where proteolysis is increased, two genes specific to muscle atrophy, MuRf1 and MAFbx, are upregulated. These encode ubiquitin ligases, which bind to and mediate ubiquitination of myofibrillar proteins for subsequent degradation during muscle atrophy.
  
  
  METHODS
  Fifteen patients undergoing leg amputation were divided into two groups. Group A included 12 elderly patients (mean age 79years) amputated for vascular disease (complicated by diabetes in four), chronic osteomyelitis or squamous cell carcinoma. Group B included three car accident victims (mean age 32years) amputated due to acute arterial insufficiency. Gastrocnemius muscle biopsies were collected for a histochemical and immunohistochemical (anti-MuRf1, anti-MAFbx) study.
  
  
  RESULTS
  Group A specimens showed a decreased cross-sectional fiber area and length, adipose tissue replacement, and MuRf1 and MAFbx immunoreactivity. Muscle cells showed MuRf1 and MAFbx subsarcolemmal immunoreactivity and weak extracellular matrix immunoreactivity. Group B samples exhibited mild muscle structural changes; they did not stain with anti-MuRf1 or anti-MAFbx, and neither did sections showing muscle degeneration and adipose tissue replacement.
  
  
  CONCLUSIONS
  Results of our preliminary study showed upregulation of MuRf1 and MAFbx in atrophied muscle and support their role as regulatory peptides in various conditions that lead to muscle atrophy. Data suggest that the study of cellular pathways can help identify promising targets for effective new treatments for skeletal muscle atrophy.
  
  
  CONCLUSIONS
  The treatment of several orthopedic conditions is complicated by muscle atrophy; potential treatments could be directed to specific sites where these proteins are localized.
authors.affiliation: Cattedra di Ortopedia e Traumatologia, Università Politecnica delle Marche, Azienda Ospedaliero-Universitaria, Ospedali Riuniti di Ancona, Via Conca, Torrette, 60100 Ancona, Italy. l.depalma@univpm.it
authors.forename: Luigi
authors.initials: L
authors.lastname: de Palma
authors.forename: Mario
authors.initials: M
authors.lastname: Marinelli
authors.forename: Matteo
authors.initials: M
authors.lastname: Pavan
authors.forename: Alessandro
authors.initials: A
authors.lastname: Orazi
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D009124:Muscle Proteins / Q000378:metabolism*; D018482:Muscle, Skeletal / Q000201:enzymology* / Q000473:pathology*; D010019:Osteomyelitis / Q000201:enzymology; D016491:Peripheral Vascular Diseases / Q000201:enzymology; D044843:SKP Cullin F-Box Protein Ligases / Q000378:metabolism*; D012508:Sarcolemma / Q000201:enzymology; D000070584:Tripartite Motif Proteins; D044767:Ubiquitin-Protein Ligases / Q000378:metabolism*; D015854:Up-Regulation / Q000502:physiology
chemical_list: D009124:Muscle Proteins; D000070584:Tripartite Motif Proteins; C440907:FBXO32 protein, human; D044843:SKP Cullin F-Box Protein Ligases; C440908:TRIM63 protein, human; D044767:Ubiquitin-Protein Ligases