Effects of Niacin Restriction on Sirtuin and PARP Responses to Photodamage in Human Skin 英文参考文献.docVIP

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Effects of Niacin Restriction on Sirtuin and PARP Responses to Photodamage in Human Skin 英文参考文献.doc

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Effects of Niacin Restriction on Sirtuin and PARP Responses to Photodamage in Human Skin 英文参考文献

EffectsofNiacinRestrictiononSirtuinandPARP ResponsestoPhotodamageinHumanSkin ClaudiaA.Benavente,StephanieA.Schnell,ElaineL.Jacobson* ArizonaCancerCenterandDepartmentofPharmacologyandToxicology,CollegeofPharmacy,TheUniversityofArizona,Tucson,Arizona,UnitedStatesofAmerica Abstract Sirtuins (SIRTs) and poly(ADP-ribose) polymerases (PARPs), NAD+-dependent enzymes, link cellular energy status with responsestoenvironmentalstresses.SkinisfrequentlyexposedtotheDNAdamagingeffectsofUVirradiation,aknown etiologyinskincancer.Thus,understandingthedefensemechanismsinresponsetoUV,includingtheroleofSIRTsand PARPs, may be important in developing skin cancer prevention strategies. Here, we report expression of the seven SIRT familymembersinhumanskin.SIRTsgeneexpressionsareprogressivelyupregulatedinA431epidermoidcarcinomacells (SIRTs1and3),actinickeratoses(SIRTs2,3,5,6,and7)andsquamouscellcarcinoma(SIRTs1–7).Photodamageinduces dynamic changes in SIRT expression with upregulation of both SIRT1 and SIRT4 mRNAs. Specific losses of SIRT proteins occur early after photodamage followed by accumulation later, especially for SIRT4. Niacin restriction, which decreases + NAD ,thesirtuinsubstrate,resultsinanincreaseinacetylatedproteins,upregulationofSIRTs2and4,increasedinherent DNAdamage,alterationsinSIRTresponsestophotodamage,abrogationofPARPactivationfollowingphotodamage,and increasedsensitivitytophotodamagethatiscompletelyreversedbyrepletingniacin.Thesedatasupportthehypothesis that SIRTs and PARPs play important roles in resistance to photodamage and identify specific SIRTs that respond to photodamageandmaybetargetsforskincancerprevention. Citation: Benavente CA, Schnell SA, Jacobson EL (2012) Effects of Niacin Restriction on Sirtuin and PARP Responses to Photodamage in Human Skin. PLoS ONE7(7):e42276.doi:10.1371/journal.pone.0042276 Editor:AndrzejT.Slominski,UniversityofTennessee,UnitedStatesofAmerica ReceivedApril8,2012;AcceptedJuly2,2012;PublishedJuly31,2012 Copyright: ?2012 Benavente et a