氧化胁迫及线粒体DNA突变与衰老的研究进展Progress in the studies of the oxidative stress and mitochondrial DNA mutations with aging
程巨龙
CHENG Ju-long (School of Pharmaceutical Engineering;
摘要(Abstract):
目的介绍氧化胁迫对线粒体的影响 ,人体线粒体DNA的结构 ,线粒体DNA点突变及缺失与衰老的关系。方法根据国内外有关文献加以综述。结果与结论线粒体是生物的能量工厂 ,是氧消耗的主要细胞器。线粒体内呼吸链产生的活性氧和自由基不断积累 ,造成对细胞及其结构功能生物大分子产生氧化胁迫 ,进而产生氧化损伤 ,促进衰老。线粒体DNA是独立于染色体之外的具有自主复制的DNA ,大量实验表明线粒体DNA(mtDNA)突变与衰老及衰老有关的衰退性疾病有关
Objective To review the progress in the studies of oxidative stress and mitochondrial DNA mutations with aging.Methods Some current data were consulted,including those in the foreign and native publications.Results and conclusion Mitochondria was an organelle to produce ATP for the cells as energy.The accumulation of reactive oxygen species and free radicals,which were produced by complexes of the electron transport system in mitochondria,resulted in the oxidative stress.The aging processes were associated with the oxidative damages caused by the elevating oxidative stress.There were many reports about the mitochondrial DNA mutations associated with the aging processes.
关键词(KeyWords):
氧化胁迫;自由基;线粒体DNA突变;衰老
oxidative stress; free radical; mitochondrial mutation; aging
基金项目(Foundation):
作者(Authors):
程巨龙
CHENG Ju-long (School of Pharmaceutical Engineering;
参考文献(References):
- [1]HarmanD .Aging:Atheorybasedonfreeradicalandradiationchemistry[J].JGerontol,1956,11:298-300.
- [2]CadenasE ,DaviesKJ.Mitochondrialfreeradicalgen eration,oxidativestress,andaging[J].FreeRadicBiolMed,2000,29(3-4):222-230.
- [3]LimPS ,ChengYM ,WeiYH .Large scalemitochon drialDNAdeletionsinskeletalmuscleofpatientswithend stagerenaldisease[J].FreeRadicBiolMed,2000,29(5):454-463.
- [4]SastreJ,PallardoFV ,GarciadelaAsuncionJ,etal.Mitochondria,oxidativestressandaging[J].FreeRadicRes,2000,32(3):189-198.
- [5]BohrVA ,DianovGL .OxidativeDNAdamageprocess inginnuclearandmitochondrialDNA [J].Biochimie,1999,81(1-2):155-160.
- [6]FischelGhodsianN .Mitochondrialdeafnessmutationsreviewed[J].HumMutat,1999,13(4):261-270.
- [7]FragaCG ,ShigenagaMK ,ParkJW ,etal.OxidativedamagetoDNAandduringaging:8 hydroxy2’ de oxyguanosineinratorganDNAandUrine[J].ProcNatlAcadSciUSA ,1990,87:4533-4537.
- [8]Muller hockerJ.Mitochondriaandaging[J].BrainPathol,1992,2:149-158.
- [9]RichterC ,ParkJ W ,AmesBN .NormaloxidativedamagetomitochondrialandnuclearDNAisextensive[J].ProcNatlAcadSciUSA ,1988,85:6465-6467.
- [10]HayakawaM ,TorriK ,SugiyamaS ,etal.Age associ atedaccumulationof8 hydroxygaanosineinmitochon drialDNAofhumandiaphragm[J].BiochemBiophysResCommun,1991,179:1023-1029.
- [11]MecocciP ,MacGarveyU ,KaufmanAE ,etal.Oxida tivedamagetomitochondrialDNAshowsmarkedage dependentincreasesinhumanbrain[J].AnnuRevNeurol,1993,34:609-616.
- [12]SouzaPintoNC ,CroteauDL ,HudsonEK ,etal.Age associatedincreasein8 oxo deoxyguanosine glycosy lase/APlyaseactivityinratmitochondria[J].NucleicAcidsRes,1999,27(8):1935-1942.
- [13]MurdockDG ,ChristacosNC ,WallaceDC .Theage re latedaccumulationofamitochondrialDNAcontrolre gionmutationinmuscle,butnotbrain,detectedbyasensitivePNA directedPCRclampingbasedmethod[J].NucleicAcidsRes,2000,28(21):4350-4355.
- [14]ShoffnerJM ,LottMT ,LezzaAMS ,etal.Myoclonicepilepsyandragged redfiberdisease(MERRF)isasso ciatedwithamitochondrialDNAtRNAlysmutation[J].Cell,1990,61:931-937.
- [15]GotoYI,NonakaI,HoraiS .AmutationinthetR NAleu(URR) geneassociatedwiththeMELASsub groupofmitochondrialencephalomyopathies[J].Na ture,1993,348:1099-1104.
- [16]KadenbachB ,MunscherC ,FrankV ,etal.Humanagingisassociatedwithstochasticmutationsofmito chondrialDNA [J].MutatRes,1995,338:161-172.
- [17]MunscherC ,Muller hockerJ,KadenbachB .HumanagingisassociatedwithvariouspointmutationsintR NAgenesofmitochondrialDNA [J].BiolChemHop perSeyler,1993,374:1099-1104.
- [18]MichikawaY ,MazzucchelliF ,BresolinN ,etal.Ag ing dependentlargeaccumulationofpointmutationsinthehumanmtDNAcontrolregionforreplication[J].Science,1999,286(5440):665.
- [19]SimonDK ,LinMT ,AhnCH ,etal.LowmutationalburdenofindividualacquiredmitochondrialDNAmu tationsinbrain[J].Genomics,2001,73(1):113-116.
- [20]WangY ,MichikawaY ,MallidisC ,etal.Muscle spe cificmutationsaccumulatewithagingincriticalhumanmtDNAcontrolsitesforreplication[J].ProcNatlA cadSciUSA ,2001,98(7):4022-4027.
- [21]AdachiK ,FujiuraY ,MayumiF ,etal.AdeletionofmitochondrialDNAinmurinedoxorubicin inducedcar diotoxicity[J].BiochemBiophysResCommun,1993,195:945-951.
- [22]WallaceDC .DiseasesofthemitochondrialDNA [J].AnnuRevBiochem,1992,61:1175-1212.
- [23]ZhangC ,BaumerA ,MaxwellRJ,etal.Multiplemi tochondrialDNAdeletionsinanelderlyhumanindivid ual[J].FEBSLetter,1992,297:34-38.
- [24]ZengZ ,ZhangZ ,YuH ,etal.MitochondrialDNAdeletionsareassociatedwithischemiaandaginginBalb/cmousebrain[J].JCellBiochem,1999,73(4):545-553.
- [25]MelovS,SchneiderJA ,CoskunPE ,etal.Mitochon drialDNArearrangementsinaginghumanbrainandinsituPCRofmtDNA [J].NeurobiolAging,1999,20(5):565-571.
- [26]KhrapkoK ,BodyakN ,ThillyWG ,etal.Cell by cellscanningofwholemitochondrialgenomesinagedhu manheartrevealsasignificantfractionofmyocyteswithclonallyexpandeddeletions[J].NucleicAcidsRes,1999,27(11):2434-2441.
- [27]LeeCM ,WeindruchR ,AikenJM .Age associatedal terationsofthemitochondrialgenome[J].FreeRadi calBiology&Medicine,1997,22:1259-1269.
- [28]CottrellDA ,BlakelyEL ,BorthwickGM ,etal.RoleofmitochondrialDNAmutationsindiseaseandaging[J].AnnNYAcadSci,2000,908:199-207.
- [29]SimonDK ,JohnsDR .Mitochondrialdisorders:clinicalandgeneticfeatures[J].AnnuRevMed,1999,50:111-127.
- [30]BerdanierCD ,EvertsHB .MitochondrialDNAinaginganddegenerativedisease[J].MutatRes,2001,475(1-2):169-183.
- [31]EnriquezJA ,CabezasHerreraJ.Veryrarecomplemen tationbetweenmitochondriacarryingdifferentmito chondrialDNAmutationspointstointrinsicgeneticau tonomyoftheorganellesinculturedhumancells[J].JBiolChem,2000,275(15):11207-11215.
- [32]ChinneryPF ,TaylorGA ,HowellN ,etal.Pointmuta tionsofthemtDNAcontrolregioninnormalandneu rodegenerativehumanbrains[J].AmJHumGenet,2001,68(2):529-532.