Effects of endotoxaemia on protein metabolism in rat fast-twitch skeletal muscle and myocardium

Andrew Murton, Nima Alamdari, Shiela M. Gardiner, Dumitru Constantin-Teodisiu, Robert Layfield, Terence Bennett, Paul L. Greenhaff

Research output: Contribution to journalArticle

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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. Methodology/Principal Findings: 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 μg 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 α1-3, 5-7 subunits of the 20S proteasome, were observed in EDL but not myocardium. In contrast, elevations in phosphorylation of p70 S6K residues Thr421/Ser424, and 4E-BP1 residues Thr37/Thr46 (P<0.05), consistent with an elevation in translation initiation, were seen exclusively in the myocardium of LPS-treated animals. Conclusions/Significance: 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.

Original languageEnglish (US)
Article numbere6945
JournalPLoS One
Volume4
Issue number9
DOIs
StatePublished - Sep 14 2009
Externally publishedYes

Fingerprint

endotoxemia
Endotoxemia
myocardium
protein metabolism
Metabolism
Muscle
skeletal muscle
Rats
Myocardium
Skeletal Muscle
rats
Proteins
protein content
Animals
Proteolysis
Phosphorylation
Catheters
Proteasome Endopeptidase Complex
Vascular Access Devices
Lipopolysaccharides

ASJC Scopus subject areas

  • Medicine(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)

Cite this

Murton, A., Alamdari, N., Gardiner, S. M., Constantin-Teodisiu, D., Layfield, R., Bennett, T., & Greenhaff, P. L. (2009). Effects of endotoxaemia on protein metabolism in rat fast-twitch skeletal muscle and myocardium. PLoS One, 4(9), [e6945]. https://doi.org/10.1371/journal.pone.0006945

Effects of endotoxaemia on protein metabolism in rat fast-twitch skeletal muscle and myocardium. / Murton, Andrew; Alamdari, Nima; Gardiner, Shiela M.; Constantin-Teodisiu, Dumitru; Layfield, Robert; Bennett, Terence; Greenhaff, Paul L.

In: PLoS One, Vol. 4, No. 9, e6945, 14.09.2009.

Research output: Contribution to journalArticle

Murton, A, Alamdari, N, Gardiner, SM, Constantin-Teodisiu, D, Layfield, R, Bennett, T & Greenhaff, PL 2009, 'Effects of endotoxaemia on protein metabolism in rat fast-twitch skeletal muscle and myocardium', PLoS One, vol. 4, no. 9, e6945. https://doi.org/10.1371/journal.pone.0006945
Murton A, Alamdari N, Gardiner SM, Constantin-Teodisiu D, Layfield R, Bennett T et al. Effects of endotoxaemia on protein metabolism in rat fast-twitch skeletal muscle and myocardium. PLoS One. 2009 Sep 14;4(9). e6945. https://doi.org/10.1371/journal.pone.0006945
Murton, Andrew ; Alamdari, Nima ; Gardiner, Shiela M. ; Constantin-Teodisiu, Dumitru ; Layfield, Robert ; Bennett, Terence ; Greenhaff, Paul L. / Effects of endotoxaemia on protein metabolism in rat fast-twitch skeletal muscle and myocardium. In: PLoS One. 2009 ; Vol. 4, No. 9.
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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. Methodology/Principal Findings: 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 μg 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 α1-3, 5-7 subunits of the 20S proteasome, were observed in EDL but not myocardium. In contrast, elevations in phosphorylation of p70 S6K residues Thr421/Ser424, and 4E-BP1 residues Thr37/Thr46 (P<0.05), consistent with an elevation in translation initiation, were seen exclusively in the myocardium of LPS-treated animals. Conclusions/Significance: 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.",
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