Control of reactive oxygen species production in contracting skeletal musclears.2011.pdf

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1、Page1of351FORUMREVIEWARTICLEControlofreactiveoxygenspeciesproductionincontractingskeletalmuscleMalcolmJ.JacksonPathophysiologyResearchUnitInstituteofAgeingandChronicDiseaseUniversityofLiverpoolLiverpoolL693GAU.K.Antioxidants&RedoxSignalingControlofreactiveoxygenspec

2、iesproductionincontractingskeletalmuscle(doi:10.1089/ars.2011.3976)Thisarticlehasbeenpeer-reviewedandacceptedforpublication,buthasyettoundergocopyeditingandproofcorrection.Thefinalpublishedversionmaydifferfromthisproof.1Page2of352AbstractTheincreasedactivitiesoffree

3、radicalsorreactiveoxygenspeciesintissuesofexercisinghumansandanimalswerefirstreported~30yearsago.Agreatdealhasbeenlearnedabouttheprocessesthatcangeneratethesemolecules,butthereislittleagreementonwhichareimportant,howtheyarecontrolledandtherearevirtuallynoquantitativ

4、edata.Superoxideandnitricoxidearegeneratedbyskeletalmuscleandtheirreactionsleadtoformationofsecondaryspecies.Aconsiderableamountisknownaboutcontrolofsuperoxidegenerationbyxanthineoxidaseactivity,butsimilarinformationforothergenerationsystemsislacking.Re-evaluationof

5、publisheddataindicatespotentialapproachestoquantificationofthehydrogenperoxideconcentrationinrestingandcontractingmusclecells.Suchcalculationsrevealthatduringcontractionsintracellularhydrogenperoxideconcentrationsinskeletalmusclemayonlyincreaseby~100nM.Theprimaryeff

6、ectsofthismodestincreaseappeartobein“redox”signalingprocessesthatmediatesomeoftheresponsesandadaptationsofAntioxidants&RedoxSignalingmuscletoexercise.Theseact,inpart,toincreasetheexpressionofcytoprotectiveproteins(e.g.heatshockproteinsandantioxidantenzymes)thathelpm

7、aintaincellviability.Duringagingthese“redox”-mediatedadaptationsfailandthiscontributestoage-relatedlossofskeletalmuscle.UnderstandingthecontrolofROSgenerationinmuscleandtheeffectofagingandsomediseasestateswillaiddesignofinterventionstomaintainmusclemassandControlofr

8、eactiveoxygenspeciesproductionincontractingskeletalmuscle(doi:10.1089/ars.2011.3976)function,butisdependentupondevelopmentofnewanalyticala