近生理條件下DNA加速氧化修飾的銅-鋅超氧化物岐化酶聚集.pdf

1、華中科技大學碩士學位論文近生理條件下DNA加速氧化修飾的銅鋅超氧化物岐化酶聚集姓名：殷俊申請學位級別：碩士專業(yè)：無機化學指導教師：劉長林20080605華中科技大學碩士學位論文華中科技大學碩士學位論文IIAbstractAmyotrophiclateralsclerosis(ALS)isoneofthemostcommonadultneurodegenerativediseaseswithunknowncauses.Thestructu

2、ralthemetalbindingvariationsinCuZnsuperoxidedismutase(SOD1)mutantshavebeenlinkedtomanykindsofneurodegenerativediseasesinparticularamyotrophiclateralsclerosisduetotheiroxidativedamageaggregation.Itiswellknownthatoxidation

3、inducedmodificationofSOD1canbeusedtomimicSOD1mutantsinvitrounderphysiologicalconditions.TheaggregationbehaviofSOD1wereexaminedunderoxidativeconditionswhichcouldmimictheeffectofmutationsreflectthepracticalprocessdoneunder

4、physiologicalconditionstoahighextent.ThepresentstudyexaminedtheoxidationinducedmodificationofSOD1inthepresenceofbateDNAcanbeusedtoacceleratethefmationofSOD1aggregatesbyaseriesofbiochemicalexperiments.Theoxidationinducedm

5、odificationofSOD1weretestedbySDSPAGE2Delectrophesis.TheresultsrevealthatthepIthehyhobicityofoxidativeSOD1areincreased.TwofmsofDNAweretestedtotriggertheoxidativeSOD1aggregationbylightscatteringdirectobservationsundervisib

6、lelighttheonefmofDNAisdoublestredDNA(dsDNA)theotherfmofDNAissinglestredDNA(ssDNA).TheresultsrevealthatdsDNAactsasatemplatefacceleratingthefmationofSOD1aggregatesisincpatedintoSOD1aggregates.AsignificantalterationinthepIt

7、hehyhobicityofSOD1causedbyoxidationtheenrichmentinSOD1alongdsDNAdoublestrsaretwomainreasonsresponsiblefDNAacceleratedSOD1aggregation.TheaccelerationeffectofSOD1aggregationinvitrouponadditionofssDNAof24nucleotideswasexami

8、nedunderphysiologicalconditions.ssDNAwastestedtotriggertheSOD1aggregationbylightscatteringdirectobservationsundervisiblelight.TheresultsrevealthatssDNAcanacceleratethefmationofssDNASOD1aggregatemonomeroligomericaggregate