title: Effects of endotoxaemia on protein metabolism in rat fast-twitch skeletal muscle and myocardium.
abstract: BACKGROUND
  It is unclear if the rat myocardium undergoes the same rapid reductions in protein content that are classically observed in fast-twitch skeletal muscle during endotoxaemia.
  
  
  RESULTS
  To investigate this further, and to determine if there is any divergence in the response of skeletal muscle and myocardium in the mechanisms that are thought to be largely responsible for eliciting changes in protein content, Sprague Dawley rats were implanted with vascular catheters and administered lipopolysaccharide (LPS; 150 microg kg(-1) h(-1)) intravenously for 2 h, 6 h or 24 h (saline administered control animals were also included), after which the extensor digitorum longus (EDL) and myocardium were removed under terminal anaesthesia. The protein-to-DNA ratio, a marker of protein content, was significantly reduced in the EDL following 24 h LPS administration (23%; P<0.05), but was no different from controls in the myocardium. At the same time point, a significant increase in MAFbx/atrogin-1 and MuRF1 mRNA (3.7+/-0.7- and 19.5+/-1.9-fold increase vs. controls, respectively; P<0.05), in addition to protein levels of alpha1-3, 5-7 subunits of the 20S proteasome, were observed in EDL but not myocardium. In contrast, elevations in phosphorylation of p70 S6K residues Thr(421)/Ser(424), and 4E-BP1 residues Thr(37)/Thr(46) (P<0.05), consistent with an elevation in translation initiation, were seen exclusively in the myocardium of LPS-treated animals.
  
  
  CONCLUSIONS
  In summary, these findings suggest that the myocardium does not undergo the same catabolic response as skeletal muscle during early endotoxaemia, partly due to the absence of transcriptional and signalling events in the myocardium typically associated with increased muscle proteolysis and the suppression of protein synthesis.
authors.affiliation: Centre for Integrated Systems Biology and Medicine, School of Biomedical Sciences, Queen's Medical Centre, University of Nottingham, Nottingham, UK. andrew.murton@nottingham.ac.uk
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: Murton
authors.forename: Nima
authors.initials: N
authors.lastname: Alamdari
authors.forename: Sheila M
authors.initials: SM
authors.lastname: Gardiner
authors.forename: Dumitru
authors.initials: D
authors.lastname: Constantin-Teodosiu
authors.forename: Robert
authors.initials: R
authors.lastname: Layfield
authors.forename: Terence
authors.initials: T
authors.lastname: Bennett
authors.forename: Paul L
authors.initials: PL
authors.lastname: Greenhaff
mesh_terms: D000818:Animals; D019446:Endotoxemia / Q000378:metabolism* / Q000503:physiopathology; D006339:Heart Rate; D008070:Lipopolysaccharides / Q000378:metabolism; D008297:Male; D008954:Models, Biological; D018656:Muscle Fibers, Fast-Twitch / Q000378:metabolism*; D009206:Myocardium / Q000378:metabolism*; D010766:Phosphorylation; D046988:Proteasome Endopeptidase Complex / Q000378:metabolism; D011506:Proteins / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction; D013997:Time Factors
chemical_list: D008070:Lipopolysaccharides; D011506:Proteins; D046988:Proteasome Endopeptidase Complex