Effects of Endotoxaemia on Protein Metabolism in Rat Fast-Twitch Skeletal Muscle and Myocardium 英文参考文献.docVIP

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Effects of Endotoxaemia on Protein Metabolism in Rat Fast-Twitch Skeletal Muscle and Myocardium 英文参考文献.doc

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Effects of Endotoxaemia on Protein Metabolism in Rat Fast-Twitch Skeletal Muscle and Myocardium 英文参考文献

EffectsofEndotoxaemiaonProteinMetabolisminRat Fast-TwitchSkeletalMuscleandMyocardium AndrewJ.Murton*,NimaAlamdari,SheilaM.Gardiner,DumitruConstantin-Teodosiu,RobertLayfield, TerenceBennett,PaulL.Greenhaff CentreforIntegratedSystemsBiologyandMedicine,SchoolofBiomedicalSciences,Queen’sMedicalCentre,UniversityofNottingham,Nottingham,UnitedKingdom Abstract Background:Itisuncleariftheratmyocardiumundergoesthesamerapidreductionsinproteincontentthatareclassically observedinfast-twitchskeletalmuscleduringendotoxaemia. Methodology/PrincipalFindings:Toinvestigatethisfurther,andtodetermineifthereisanydivergenceintheresponseof 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; 150mgkg21h21)intravenouslyfor2h,6hor24h(salineadministeredcontrolanimalswerealsoincluded),afterwhichthe extensordigitorumlongus(EDL)andmyocardiumwereremovedunderterminalanaesthesia.Theprotein-to-DNAratio,a markerofproteincontent,wassignificantlyreducedintheEDLfollowing24hLPSadministration(23%;P,0.05),butwas nodifferentfromcontrolsinthemyocardium.Atthesametimepoint,asignificantincreaseinMAFbx/atrogin-1andMuRF1 mRNA (3.760.7- and 19.561.9-fold increase vs. controls, respectively; P,0.05), in addition to protein levels of a1-3, 5–7 subunitsofthe20Sproteasome,wereobservedinEDLbutnotmyocardium.Incontrast,elevationsinphosphorylationof p70 S6K residues Thr421/Ser424, and 4E-BP1 residues Thr37/Thr46 (P,0.05), consistent with an elevation in translation initiation,wereseenexclusivelyinthemyocardiumofLPS-treatedanimals. Conclusions/Significance:Insummary,thesefindingssuggestthatthemyocardiumdoesnotundergothesamecatabolic responseasskeletalmuscleduringearlyendotoxaemia,partlyduetotheabsenceoftranscriptionalandsignallingeventsin themyocardiumtypicallyassociatedwithincreasedmuscleproteolysisandthesuppressionofproteinsynthesis. Citation