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. 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. © 2009 Murton et al.