title: Thermal injury activates the eEF2K-dependent eEF2 pathway in pediatric patients.
abstract: BACKGROUND
  Burn induces a hypermetabolic state characterized by alterations in protein metabolism, which is associated with increased morbidity and mortality. Eukaryotic elongation factor 2 (eEF2) plays a crucial role in regulating protein synthesis in many diseases, but whether it participates in burn-induced hypermetabolism is unclear. The aim of this study was to determine the expression of eEF2 and the upstream eEF2-inactivating kinase, eEF2K, in severely burned pediatric patients.
  
  
  METHODS
  Eight pediatric patients (> 40% total body surface area) and 3 nonburned pediatric volunteers were enrolled. Muscle and skin biopsies were collected at early (0-10 days postburn [dpb]), middle (11-49 dpb), and late (50-365 dpb) time points. Resting energy expenditure (REE), body composition, and muscle protein fractional synthesis rate (FSR) were measured. Proteins were extracted and analyzed by Western blotting. To further investigate the protein synthesis pathway, microarray data from muscle and skin were examined from 22 nonburned and 20 burned children.
  
  
  RESULTS
  Burn patients exhibited a profound hypermetabolic response, as seen by a significant increase in REE (P < .05) and loss of lean body mass without altered muscle FSR, indicating a shift to catabolism after thermal injury. In muscle, the phosphorylation of eEF2K-dependent eEF2 was down regulated early and middle postburn. Similar changes in eEF2K and eEF2 levels occurred in skin at the early time point. Total amounts of eEF2 and eEF2K were not altered.
  
  
  CONCLUSIONS
  Burn induces prolonged activation of eEF2K and eEF2. Alterations in these mediators may contribute to profound hypermetabolism in severely burned patients.
authors.affiliation: Department of Surgery, University of Texas Health Science Center at San Antonio, San Antonio, Texas, USA.
authors.forename: Juquan
authors.initials: J
authors.lastname: Song
authors.forename: Celeste C
authors.initials: CC
authors.lastname: Finnerty
authors.forename: David N
authors.initials: DN
authors.lastname: Herndon
authors.forename: Robert
authors.initials: R
authors.lastname: Kraft
authors.forename: Darren
authors.initials: D
authors.lastname: Boehning
authors.forename: Natasha C
authors.initials: NC
authors.lastname: Brooks
authors.forename: Ronald G
authors.initials: RG
authors.lastname: Tompkins
authors.forename: Marc G
authors.initials: MG
authors.lastname: Jeschke
mesh_terms: D000293:Adolescent; D015153:Blotting, Western; D001823:Body Composition; D001830:Body Surface Area; D002056:Burns / Q000378:metabolism* / Q000503:physiopathology; D002153:Calorimetry, Indirect / Q000379:methods; D002648:Child; D002675:Child, Preschool; D015536:Down-Regulation; D054736:Elongation Factor 2 Kinase / Q000235:genetics / Q000378:metabolism*; D004734:Energy Metabolism; D005260:Female; D023281:Genomics; D006801:Humans; D007223:Infant; D008297:Male; D009124:Muscle Proteins / Q000096:biosynthesis; D018482:Muscle, Skeletal / Q000378:metabolism; D020652:Peptide Elongation Factor 2 / Q000235:genetics / Q000378:metabolism*; D010766:Phosphorylation; D012146:Rest; D015398:Signal Transduction
chemical_list: D009124:Muscle Proteins; D020652:Peptide Elongation Factor 2; C517689:EEF2K protein, human; D054736:Elongation Factor 2 Kinase