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1、CellularSignalling14(2002)879–897www.elsevier.com/locate/cellsigReviewarticleAntioxidantandprooxidantmechanismsintheregulationofredox(y)-sensitivetranscriptionfactorsJohnJ.Haddad*Severinghaus-RadiometerResearchLaboratories,MolecularNeuroscienceResearchDivision,DepartmentofAnesthesia
2、andPerioperativeCare,UniversityofCaliforniaatSanFrancisco,SchoolofMedicine,MedicalSciencesBuildingS-261,513ParnassusAvenue,SanFrancisco,CA94143-0542,USAReceived2April2002;accepted13May2002AbstractAprogressiveriseofoxidativestressduetothealteredreduction–oxidation(redox)homeostasisap
3、pearstobeoneofthehallmarksoftheprocessesthatregulategenetranscriptioninphysiologyandpathophysiology.Reactiveoxygen(ROS)andnitrogen(RNS)speciesserveassignalingmessengersfortheevolutionandperpetuationoftheinflammatoryprocessthatisoftenassociatedwiththeconditionofoxidativestress,whichi
4、nvolvesgeneticregulation.ChangesinthepatternofgeneexpressionthroughROS/RNS-sensitiveregulatorytranscriptionfactorsarecrucialcomponentsofthemachinerythatdeterminescellularresponsestooxidative/redoxconditions.Transcriptionfactorsthataredirectlyinfluencedbyreactivespeciesandpro-inflamm
5、atorysignalsincludenuclearfactor-nB(NF-nB)andhypoxia-induciblefactor-1a(HIF-1a).Here,Idescribethebasiccomponentsoftheintracellularoxidative/redoxcontrolmachineryanditscrucialregulationofoxygen-andredox-sensitivetranscriptionfactorssuchasNF-nBandHIF-1a.D2002ElsevierScienceInc.Allrigh
6、tsreserved.Keywords:Antioxidant;HIF-1a;NF-nB;Oxygen;Redox;TranscriptionfactorsAbbreviations:NAC,N-acetyl-L-cysteine;AP-1,activatingprotein-1;1.IntroductionASK,apoptosissignal-inducingkinase;ATF,activatingtranscriptionfactor;ATP,Adenosinetriphosphate;AOP,anti-oxidativepotential;ARE,a
7、ntiox-Molecularoxygenisanimportantenvironmentalandidantresponsiveelement;ARDS,adultsrespiratorydistresssyndrome;developmentalsignalthatregulatescellularenergetics,ARNT,arylhydrocarbonnucleartranslocator;bHLH,basichelix–loop–growthanddifferentiation[1–4].Despiteitscentralrolehelix;BC
8、NU,1,3-bis-(2-chlor
