Bicarbonate Plays a Critical Role in the Generation of Cytotoxicity during SIN-1 Decomposition in Culture Medium英文文献资料.docVIP

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Bicarbonate Plays a Critical Role in the Generation of Cytotoxicity during SIN-1 Decomposition in Culture Medium英文文献资料.doc

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Bicarbonate Plays a Critical Role in the Generation of Cytotoxicity during SIN-1 Decomposition in Culture Medium英文文献资料

HindawiPublishingCorporation OxidativeMedicineandCellularLongevity Volume2012,ArticleID326731,15pages doi:10.1155/2012/326731 ResearchArticle BicarbonatePlaysaCriticalRoleintheGenerationof CytotoxicityduringSIN-1DecompositioninCultureMedium KyoShirai,TatsumiOkada,KanakoKonishi,HiroshiMurata,SoichiroAkashi, FumioSugawara,NobuoWatanabe,andTakaoArai DepartmentofAppliedBiologicalScience,FacultyofScienceandTechnology,TokyoUniversityofScience,2641Yamazaki, Noda,Chiba278-8510,Japan CorrespondenceshouldbeaddressedtoNobuoWatanabe,nwatanab@rs.noda.tus.ac.jp Received30March2012;Accepted14May2012 AcademicEditor:DanielaGiustarini Copyright?2012KyoShiraietal.ThisisanopenaccessarticledistributedundertheCreativeCommonsAttributionLicense, whichpermitsunrestricteduse,distribution,andreproductioninanymedium,providedtheoriginalworkisproperlycited. 3-Morpholinosydnonimine(SIN-1)isusedasadonorofperoxynitrite(ONOO that,thecell-culturemediumremainscytotoxictoPC12cellsevenafteralmostcompleteSIN-1decomposition,suggestingthat reactionproduct(s)inthemedium,ratherthanONOO ,exertcytotoxice?ects.Here,weclari?edthatsigni?cantcytotoxicity ? )invariousstudies.Wedemonstrated,however, ? persists after SIN-1 decomposes in bicarbonate, a component of the culture medium, but not in NaOH. Cytotoxic SIN-1- decomposedbicarbonate,whichlacksbothoxidizingandnitrosatingactivities,degradestoinnocuousstateovertime.Theextent of SIN-1 cytotoxicity, irrespective of its fresh or decomposed state, appears to depend on the total number of initial SIN-1 moleculespercell,ratherthanitsconcentration,andinvolvesoxidative/nitrosativestress-relatedcelldamage.Theseresultssuggest that,despiteitslowabundance,thebicarbonate-dependentcytotoxicsubstancethataccumulatesinthemediumduringSIN-1 breakdownisthecytotoxicentityofSIN-1. 1.Introduction ? ONOO ,3-morpholinosydnonimine(SIN-1)iswidelyused asanONOO? donorforvariousstudies(Figure1).SIN-1 Nitric oxide (NO) is produced from L arginine in various tissuesbyNOsynthases(NOSs),andi