mutations of tp53 gene and oxidative stressin alzheimer’s disease patients

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1、MutationsofTP53GeneandOxidativeStressinAlzheimer’sDiseasePatientsMutationsofTP53GeneandOxidativeStressinAlzheimer’sDiseasePatientsJolantaDorszeentofNeurology,PoznanUniversityofMedicalSciences,Poznan,Poland2DepartmentofBiochemistryandMolecularBiology,PoznanUniversityofMedicalSciences,Po

2、znan,Poland3ChairandDepartmentofNeurology,PoznanUniversityofMedicalSciences,10,FredryStr.,61-701Poznan,PolandEmail:*dorszeber2013;revised13January2014;accepted31January2014Copyright©2014byauthorsandScientificResearchPublishingInc.ThisonsAttributionInternationalLicense(CCBY).creati

3、vemons.org/licenses/by/4.0/AbstractAlzheimer’sdisease(AD)leadstothegenerationofβ-amyloid(Aβ),aydamageDNAandthusleadtoapoptosisinductionbythep53pathaythenbeconnectedentofAD.Studiesutationsinexon7edonDNAisolatedfromicalparametersintheperipherallymphocytesoftheseindividuals.Ourstudyshouta

4、tionTP53C708T(21%)[p<0.05]andamissensemutationTP53C748A(4%)onlyintheADpatients.Moreover,inADpatientsutation,thelevelof8-oxo-2’-deoxyguanosine(8-oxo2dG)orethan5timeshigherthantheaveragelevelinthisstudygroup.InADpatientsilarinADpatientsutationandtheutationsinexon7ofTP53(C748A,C708T)ma

5、ybeassociateder’sdisease(AD)isoneofthemostimportantneurodegenerativediseases.Anumberoffactorsarein-*Correspondingauthor.J.Dorszeyloidprecursorprotein(APP).MutationsintheAPPgeneaccountforfamilialAD(FAD)yloid(Aβ)levelintheprocessingofthisgene[1].AnelevatedlevelofAβmaygeneratefreeradicals

6、,aythenoxidizemacromolecules,suchasDNA[2]-[5].AmongthemarkersofoxidativeDNAmodifications,8-oxo-2’-deoxyguanosine(8-oxo2dG)isthemostabundantproductofhydroxyl-inducedoxidationinthepurinebasesofnucleicacids.Variablelevelsof8-oxo2dGhavebeenshophocytesofADpatients[8][9].Furthermore,ithasbee

7、ndemonstratedthatinhumans,8-oxoguanineDNAglycosylase1(OGG1)isthemainDNArepairenzymethatexcises8-oxo2dGfromDNA[9].AstudybyDorszesofOGG-1a,1b,and1cchangestothelevelsof8-oxo2dGintheperipheralbloodlymphocytesofADpatients.Itayleadtohigherbackgroundmutationfrequency,e.g.GC→AT[10].Thistypeo