RNA Oxidation Adducts 8-OHG and 8-OHA Change with Aβ42 Levels in Late-Stage Alzheimers Disease 英文参考文献.docVIP

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RNA Oxidation Adducts 8-OHG and 8-OHA Change with Aβ42 Levels in Late-Stage Alzheimers Disease 英文参考文献.doc

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RNA Oxidation Adducts 8-OHG and 8-OHA Change with Aβ42 Levels in Late-Stage Alzheimers Disease 英文参考文献

RNAOxidationAdducts8-OHGand8-OHAChangewith Ab42 LevelsinLate-StageAlzheimer’sDisease AdamM.Weidner1,2.,MelissaA.Bradley1,2.,TinaL.Beckett1.,DanaM.Niedowicz1,2,AmyL.S. Dowling1,4,SergeyV.Matveev1,HarryLeVine III1,2,MarkA.Lovell1,3*,M.PaulMurphy1,2 * 1Sanders-BrownCenteronAging,UniversityofKentucky,Lexington,Kentucky,UnitedStatesofAmerica,2DepartmentofMolecularandCellularBiochemistry,University of Kentucky, Lexington, Kentucky, United States of America, 3Department of Chemistry, University of Kentucky, Lexington, Kentucky, United States of America, 4DepartmentofMolecularandBiomedicalPharmacology,UniversityofKentucky,Lexington,Kentucky,UnitedStatesofAmerica Abstract Whileresearchsupportsamyloid-b(Ab)astheetiologicagentofAlzheimer’sdisease(AD),themechanismofactionremains unclear. Evidence indicates that adducts of RNA caused by oxidation also represent an early phenomenon in AD. It is currently unknown what type of influence these two observations have on each other, if any. We quantified five RNA adductsbygaschromatography/massspectroscopyacrossfivebrainregionsfromADcasesandage-matchedcontrols.We thenusedareductivedirectedanalysistocomparetheRNAadductstocommonindicesofADneuropathologyandvarious poolsofAb.Usingdatafromfourdisease-affectedbrainregions(Brodmann’sArea9,hippocampus,inferiorparietallobule, andthesuperiorandmiddletemporalgyri),wefoundthattheRNAadduct8-hydroxyguanine(8-OHG)decreased,while8- hydroxyadenine(8-OHA)increasedinAD.Thecerebellum,whichisgenerallysparedinAD,didnotshowdiseaserelated changes,andnoRNAadductscorrelatedwiththenumberofplaquesortangles.Multipleregressionanalysisrevealedthat SDS-soluble Ab42 was the best predictor of changes in 8-OHG, while formic acid-soluble Ab42 was the best predictor of changesin8-OHA.ThisstudyindicatesthatalthoughthereisaconnectionbetweenADrelatedneuropathologyandRNA oxidation,thisrelationshipisnotstraightforward. Citation:WeidnerAM,BradleyMA,BeckettTL,NiedowiczDM,DowlingALS,etal.(2011)RNAOxidationAdducts8-OHGand8-OH