Cardiac PPAR Protein Expression is Constant as Alternate Nuclear Receptors and PGC-1 Coordinately Increase During the Postnatal Metabolic Transition英文文献资料.docVIP

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Cardiac PPAR Protein Expression is Constant as Alternate Nuclear Receptors and PGC-1 Coordinately Increase During the Postnatal Metabolic Transition英文文献资料.doc

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Cardiac PPAR Protein Expression is Constant as Alternate Nuclear Receptors and PGC-1 Coordinately Increase During the Postnatal Metabolic Transition英文文献资料

HindawiPublishingCorporation PPARResearch Volume2008,ArticleID279531,8pages doi:10.1155/2008/279531 ResearchArticle CardiacPPARαProteinExpressionisConstantasAlternate NuclearReceptorsandPGC-1CoordinatelyIncreaseDuring thePostnatalMetabolicTransition NormanE.Buroker,Xue-HanNing,andMichaelPortman DepartmentofCardiology,Children’sHospitalandRegionalMedicalCenter,4800SandPointWayN.E.,Seattle,WA98105,USA CorrespondenceshouldbeaddressedtoMichaelPortman,michael.portman@ Received20June2007;Accepted22July2007 RecommendedbyBrianN.Finck Geneexpressiondataobtainedinmouseheartindicatethatincreasedexpressionforthenuclearreceptor,peroxisomalprolif- eratoractivatedreceptorα(PPARα),promptsthepostnataltransitionfrompredominantlycarbohydratetofattyacidoxidation preference.However,nophenotypicorproteomicdataareavailabletocon?rmdownstreamsignalingandmetabolictransition inmice.Westudiedthehypothesisthatshiftsinnuclearreceptorexpressiontriggerthenewbornmetabolicswitchinanewborn sheep.Thisspeciesiswellcharacterizedwithregardstodevelopmentalchangesinsubstrateoxidativemetabolism.Hearttissues fromfetal(130daysgestation),newborn≤24hours,and30-dayoldlambswereevaluatedforproteinexpressionfrommultiple enzymescontrollingoxidativemetabolismaswellasprincipalnuclearreceptorsandcoactivators.Althoughmuscleandlivertype carnitinepalmitoyltransferasesIshowednosigni?cantchangestocorrespondtothemetabolictransition,hexokinaseIIprotein contentshowedaprofoundtransientdrop,andpyruvatedehydrogenasekinasesteadilyincreased.PPARαshowednoincreases precedingorduringthetransition,whileperoxisomalproliferatoractivatedreceptorgammacoactivator-1(PGC-1)increasedap- proximately20-foldtransientlyinnewbornheartinconjunctionwithsigni?cantincreasesinthyroidhormonereceptorα 1and retinoid-activatedreceptorα.ThesedatachallengetheparadigmthatincreasesinPPARαpromptthepostnatalmetabolicswitch, andsuggestthatothernuclearreceptorsplayamajorrole.Asthyroidhormone(TH)modulatesPGC-1expressioninsheepduring development,thesedatafurthersug