SIRT1的生理作用及调控机制的研究进展-王晓凯

··SIRT1DOI10．3877/[e-mail]2silentinformationregulator2Sir2NAD+。Sir2、、。IvySir21。Sir22。2000Sir2SirtuinSIRT3。7Sir24。SirtuinSirtuinSIRT1～75。Sir2cDNASIRT1、SIRT2、SIRT3、SIRT4、SIRT5、SIRT6、SIRT710、19、11、12、6、19、17Sir2SIRT1Sir26。SIRT1Wnt、Notchforkhead-boxtranscriptionfactorsFOXO1/3/4、c-myc、NF-κB、IGFBP1、p300、p53、、、。SIRT1。SIRT1。、1.SIRT1199910q21.369644427～6967814733.72kb。cDNA2.4kbORFopenreadingframe974781.7kDa7。2.SIRT1、SIRT6、SIRT7SIRT6SIRT7SIRT3、SIRT4、SIRT5SIRT2。Michishita4SIRTSIRT1。、、、、。SIRT1。SIRT1。SIRT112.5d。Tanno8SIRT1SIRT1。SIRT1B1。Hisahara9SIRT1SIRT1SIRT1。SIRT1。、siRNASIRT1Tuj1。SIRT1。、Sir2、DNA、、、、。SIRTSir2。7SIRTSIRT1ⅢNAD+。FOXO1/3/4、c-myc、NF-κB、SUV39H1、p300、p53、PGC-1b、H1、H3、H4、B-Catenin、CRTC2、PARP1UCP2/3IGFBP1NCOR、PPARa、HIC1、TLE1、CLOCK、DBC110。11-12、p5313-14、FOXO15-16、BRCA117、Ku7018PGC-1a19。SIRT1。1.FOXO。、、20。SIRT1FOXO。DNAG1/SDNA。p53G1/S。p53·5137·201112524ChinJCliniciansElectronicEditionDecember152011Vol．5No．24p53SIRT1。G1/SDNA。SIRT1p53SIRT1。2.SIRT121。SIRT1COX22。SIRT1。SIRT1p5323-24。p53DNA。DNASIRT1p5338224。p53DNASIRT1p53。90%p53SIRT1SIRT1。SIRT2～7p534。SIRT1。SIRT1。Yu25、WldSNADSIRT1NAD。3.NF-κBP65P50IKB-a/bNF-κB。、、IKBNF-κB。Kang26ikkbikk、IKBNF-κB。NF-κB。SIRT1NF-κBRelA/p65NF-κBNF-κBTNF-α、IL-1β。NF-κB。NF-κBβ。SIRT1βNF-κB22。SIRT1COX-2COX27。4.reactiveoxyzenspeciesROS。ROSiNOSinducing-NOsynthaseCOX-2。NODNA28-31COX-2。Wang32ROSicariinSIRT1ROS。SIRT1。Chae33SIRT1SIRT1PTEN/JNK/FOXO1。FOXO4FOXOFOXO1、FOXO2、FOXO03FOXO4。、、。Yang34SIRT1FOXO1FHL2fourandahalfLIM2FOXO1SIRT1FOXO1。Csiszar35caloricrestrictionCRTNF-αROSNF-κB。siRNASIRT1SIRT1ROS。5.、。、。。。SIRT1uncouplingprotein2UCP2UCP2。Frescas36SIRT1FOXO1FOXO1FOXO1。SIRT1PGC-1αPPAR-γ1γ119。Lagouge37SIRT1sirt1。6.SIRT1SIRT19。SIRT1Hes-1。nuclearreceptorcorepressorN-CoR38。N-CoRSIRT1Hes1N-CoRSIRT1·6137·201112524ChinJCliniciansElectronicEditionDecember152011Vol．5No．24SIRT1N-CoR9。Sugino39SIRT1NGF。SIRT1SIRT1。SIRT1NAD20μmol/L50μmol/LNADNAD。SIRT1NicotinamideSplitomicinSIRT1。SIRT1。7.40。。9。Wu41AMPK/SIRT1。。AMPKSIRT1LC3-ⅡLC3-3。AMPKSIRT1。beclin14h3d21d。beclin142。LC3-ⅡsiRNASIRT1LC3-Ⅱ。SIRT143。、SIRT1、、、、、、、。。1LuSPLinSJ．RegulationofYeastSirtuinsbyNAD+MetabolismandCalorieRestriction．BiochimBiophysActa201018041567-1575．2．Sir2．20066822-826．3．SIRT6．200626308-310．4MichishitaEParkJYBurneskisJMetal．EvolutionarilyconservedandnonconservedcellularlocalizationsandfunctionsofhumanSIRTpro-teins．MolBiolCell2005164623-4635．5OuteiroTFKontopoulosEAltmannSMetal．Sirtuin2inhibitorsrescuealpha-synuclein-mediatedtoxicityinmodelsofParkinson'sdisease．Sci-ence2007317516-519．6RobertsARBlewittMEYoungsonNAetal．ReduceddosageofthemodifiersofepigeneticreprogrammingDnmt1Dnmt3LSmcHD1andFoxo3ahasnodetectableeffectonmousetelomerelengthinvivo．Chromosoma2011120377-385．7Voelter-MahlknechtSMahlknechtU．CloningchromosomalcharacterizationandmappingoftheNAD-dependenthistonedeaeetylasesgenesirtuin1．IntJMolMed20061759-67．8TannoMSakamotoJMiuraTetal．NucleocytoplasmicshuttlingoftheNAD+-dependenthistonedeacetylaseSIRT1．JBidChem20072826823-6832．9HisaharaSChibaSMatsumotoHetal．HistonedeacetylaseSIRT1modulatesneuronaldifferentiationbyitsnucleartranslocation．PNAS200810515599-15604．10BaurJA．BiochemicaleffectsofSIRT1activators．BiochimBiophysActa201018041626-1634．11HeHYuFXSunCetal．CBP/p300andSIRT1areinvolvedintranscriptionalregulationofS-phasespecifichistonegenes．PLoSOne20116e22088．12VaqueroAScherMErdjument-BromageHetal．SIRT1regulatesthehistonemethyl-transferaseSUV39H1duringheterochromatinformation．Na-ture2007450440-444．13KumeSHanedaMKanasakiKetal．Silentinformationregulator2SIRT1attenuatesoxidativestress-inducedmesangialcellapoptosisviap53deacetylation．FreeRadicBiolMed2006402175-2182．14ElangovanSRamachandranSVenkatesanNetal．SIRT1isessentialforoncogenicsignalingbyestrogen/estrogenreceptoralphainbreastcancer．CancerRes2011．15ZhaoWKruseJPTangYetal．NegativeregulationofthedeacetylaseSIRT1byDBC1．Nature2008451587-590．16RizkiGIwataTNLiJetal．TheEvolutionarilyConservedLongevityDeterminantsHCF-1andSIR-2.1/SIRT1CollaboratetoRegulateDAF-16/FOXO．PLoSGenet20117e1002235．17RusinMZajkowiczAButkiewiczD．Resveratrolinducessenescence-likegrowthinhibitionofU-2OScellsassociatedwiththeinstabilityoftelo-mericDNAandupregulationofBRCA1．MechAgeingDev2009130528-537．18HillSMFraschTXiangSetal．Molecularmechanismsofmelatoninanticancereffects．IntegrCancerTher20098337-346．19RodgersJTLerinCHaasWetal．NutrientcontrolofglucosehomeostasisthroughacomplexofPGC-1alphaandSIRT1．Nature2005434113-·7137·201112524ChinJCliniciansElectronicEditionDecember152011Vol．5No．24118．20LamEWFrancisREPetkovicM．FOXOtranscriptionfactorskeyregulatorsofcellfate．BiochemSocTrans200634722-726．21．Sirt1．200917144-148．22ChenJZhouYMueller-SteinerSetal．SIRT1protectsagainstmicroglia-dependentamyloid-betatoxicitythroughinhibitingNF-κBsignaling．JBiolChem200528040364-40374．23RajendranRGarvaRKrstic-DemonacosMetal．Sirtuinsmoleculartrafficlightsinthecrossroadofoxidativestresschromatinremodelingandtranscription．JBiomedBiotechnol2011．24RahmanSIslamR．MammalianSirt1insightsonitsbiologicalfunctions．CellCommunSignal20