{"@context":{"@vocab":"https://cir.nii.ac.jp/schema/1.0/","rdfs":"http://www.w3.org/2000/01/rdf-schema#","dc":"http://purl.org/dc/elements/1.1/","dcterms":"http://purl.org/dc/terms/","foaf":"http://xmlns.com/foaf/0.1/","prism":"http://prismstandard.org/namespaces/basic/2.0/","cinii":"http://ci.nii.ac.jp/ns/1.0/","datacite":"https://schema.datacite.org/meta/kernel-4/","ndl":"http://ndl.go.jp/dcndl/terms/","jpcoar":"https://github.com/JPCOAR/schema/blob/master/2.0/"},"@id":"https://cir.nii.ac.jp/crid/1360565166126078592.json","@type":"Article","productIdentifier":[{"identifier":{"@type":"DOI","@value":"10.1016/j.taap.2009.03.005"}},{"identifier":{"@type":"URI","@value":"https://api.elsevier.com/content/article/PII:S0041008X0900115X?httpAccept=text/xml"}},{"identifier":{"@type":"URI","@value":"https://api.elsevier.com/content/article/PII:S0041008X0900115X?httpAccept=text/plain"}},{"identifier":{"@type":"PMID","@value":"19303893"}},{"identifier":{"@type":"HANDLE","@value":"10146/76774"}},{"identifier":{"@type":"HANDLE","@value":"10588/597e36ce-04e5-465a-be21-1a070b6e0af6"}}],"resourceType":"学術雑誌論文(journal article)","dc:title":[{"@value":"Transcription factor Nrf2 mediates an adaptive response to sulforaphane that protects fibroblasts in vitro against the cytotoxic effects of electrophiles, peroxides and redox-cycling agents"}],"description":[{"notation":[{"@value":"Sulforaphane can stimulate cellular adaptation to redox stressors through transcription factor Nrf2. Using mouse embryonic fibroblasts (MEFs) as a model, we show herein that the normal homeostatic level of glutathione in Nrf2(-/-) MEFs was only 20% of that in their wild-type counterparts. Furthermore, the rate of glutathione synthesis following its acute depletion upon treatment with 3 micromol/l sulforaphane was very substantially lower in Nrf2(-/-) MEFs than in wild-type cells, and the rebound leading to a approximately 1.9-fold increase in glutathione that occurred 12-24 h after Nrf2(+/+) MEFs were treated with sulforaphane was not observed in Nrf2(-/-) fibroblasts. Wild-type MEFs that had been pre-treated for 24 h with 3 micromol/l sulforaphane exhibited between 1.4- and 3.2-fold resistance against thiol-reactive electrophiles, including isothiocyanates, alpha,beta-unsaturated carbonyl compounds (e.g. acrolein), aryl halides and alkene epoxides. Pre-treatment of Nrf2(+/+) MEFs with sulforaphane also protected against hydroperoxides (e.g. cumene hydroperoxide, CuOOH), free radical-generating compounds (e.g. menadione), and genotoxic electrophiles (e.g. chlorambucil). By contrast, Nrf2(-/-) MEFs were typically approximately 50% less tolerant of these agents than wild-type fibroblasts, and sulforaphane pre-treatment did not protect the mutant cells against xenobiotics. To test whether Nrf2-mediated up-regulation of glutathione represents the major cytoprotective mechanism stimulated by sulforaphane, 5 micromol/l buthionine sulfoximine (BSO) was used to inhibit glutathione synthesis. In Nrf2(+/+) MEFs pre-treated with sulforaphane, BSO diminished intrinsic resistance and abolished inducible resistance to acrolein, CuOOH and chlorambucil, but not menadione. Thus Nrf2-dependent up-regulation of GSH is the principal mechanism by which sulforaphane pre-treatment induced resistance to acrolein, CuOOH and chlorambucil, but not menadione."}]}],"creator":[{"@id":"https://cir.nii.ac.jp/crid/1380847869282367618","@type":"Researcher","foaf:name":[{"@value":"Larry G. Higgins"}]},{"@id":"https://cir.nii.ac.jp/crid/1380847869282367617","@type":"Researcher","foaf:name":[{"@value":"Michael O. Kelleher"}]},{"@id":"https://cir.nii.ac.jp/crid/1380847869282367619","@type":"Researcher","foaf:name":[{"@value":"Ian M. Eggleston"}]},{"@id":"https://cir.nii.ac.jp/crid/1420564276181587968","@type":"Researcher","personIdentifier":[{"@type":"KAKEN_RESEARCHERS","@value":"10323289"},{"@type":"NRID","@value":"1000010323289"},{"@type":"NRID","@value":"9000283423466"},{"@type":"NRID","@value":"9000001731653"},{"@type":"NRID","@value":"9000413926843"},{"@type":"NRID","@value":"9000257942412"},{"@type":"NRID","@value":"9000016851644"},{"@type":"NRID","@value":"9000413493013"},{"@type":"NRID","@value":"9000412335242"},{"@type":"NRID","@value":"9000253177257"},{"@type":"NRID","@value":"9000107386802"},{"@type":"NRID","@value":"9000413525391"},{"@type":"NRID","@value":"9000413533792"},{"@type":"NRID","@value":"9000404122023"},{"@type":"NRID","@value":"9000017038153"},{"@type":"NRID","@value":"9000004734074"},{"@type":"NRID","@value":"9000413493046"},{"@type":"NRID","@value":"9000399343863"},{"@type":"NRID","@value":"9000347049802"},{"@type":"NRID","@value":"9000413531758"},{"@type":"NRID","@value":"9000391983441"},{"@type":"NRID","@value":"9000359874069"},{"@type":"NRID","@value":"9000291598109"},{"@type":"NRID","@value":"9000411033788"},{"@type":"NRID","@value":"9000283421577"},{"@type":"RESEARCHMAP","@value":"https://researchmap.jp/read0162927"}],"foaf:name":[{"@value":"Ken Itoh"}]},{"@id":"https://cir.nii.ac.jp/crid/1420845751162485632","@type":"Researcher","personIdentifier":[{"@type":"KAKEN_RESEARCHERS","@value":"50166823"},{"@type":"NRID","@value":"1000050166823"},{"@type":"NRID","@value":"9000018475185"},{"@type":"NRID","@value":"9000399797713"},{"@type":"NRID","@value":"9000415041270"},{"@type":"NRID","@value":"9000413926842"},{"@type":"NRID","@value":"9000283733078"},{"@type":"NRID","@value":"9000253172984"},{"@type":"NRID","@value":"9000386308263"},{"@type":"NRID","@value":"9000018774612"},{"@type":"NRID","@value":"9000018561688"},{"@type":"NRID","@value":"9000413536520"},{"@type":"NRID","@value":"9000413493018"},{"@type":"NRID","@value":"9000345403324"},{"@type":"NRID","@value":"9000253177259"},{"@type":"NRID","@value":"9000000311019"},{"@type":"NRID","@value":"9000107386805"},{"@type":"NRID","@value":"9000023358348"},{"@type":"NRID","@value":"9000413519827"},{"@type":"NRID","@value":"9000413533795"},{"@type":"NRID","@value":"9000404122024"},{"@type":"NRID","@value":"9000391945105"},{"@type":"NRID","@value":"9000292880768"},{"@type":"NRID","@value":"9000391607704"},{"@type":"NRID","@value":"9000253169908"},{"@type":"NRID","@value":"9000398150759"},{"@type":"NRID","@value":"9000414259852"},{"@type":"NRID","@value":"9000002039755"},{"@type":"NRID","@value":"9000010973297"},{"@type":"NRID","@value":"9000016392585"},{"@type":"NRID","@value":"9000392826732"},{"@type":"NRID","@value":"9000283731701"},{"@type":"NRID","@value":"9000402615290"},{"@type":"NRID","@value":"9000283280261"},{"@type":"NRID","@value":"9000257873366"},{"@type":"NRID","@value":"9000408605701"},{"@type":"NRID","@value":"9000413489102"},{"@type":"NRID","@value":"9000253180478"},{"@type":"NRID","@value":"9000409464535"},{"@type":"NRID","@value":"9000413535407"},{"@type":"NRID","@value":"9000413493053"},{"@type":"NRID","@value":"9000253170320"},{"@type":"NRID","@value":"9000415124192"},{"@type":"NRID","@value":"9000412643244"},{"@type":"NRID","@value":"9000413501418"},{"@type":"NRID","@value":"9000404481581"},{"@type":"NRID","@value":"9000409850174"},{"@type":"NRID","@value":"9000253175912"},{"@type":"NRID","@value":"9000413531759"},{"@type":"NRID","@value":"9000391606189"},{"@type":"NRID","@value":"9000019220026"},{"@type":"NRID","@value":"9000017191311"},{"@type":"NRID","@value":"9000406227147"},{"@type":"NRID","@value":"9000019158360"},{"@type":"NRID","@value":"9000000605547"},{"@type":"NRID","@value":"9000261042142"},{"@type":"NRID","@value":"9000413949493"},{"@type":"NRID","@value":"9000341541854"},{"@type":"NRID","@value":"9000311504487"},{"@type":"NRID","@value":"9000406035283"},{"@type":"NRID","@value":"9000408803600"},{"@type":"NRID","@value":"9000006264205"},{"@type":"NRID","@value":"9000413535219"},{"@type":"NRID","@value":"9000253179301"},{"@type":"NRID","@value":"9000412316450"},{"@type":"NRID","@value":"9000283421578"},{"@type":"NRID","@value":"9000413512019"},{"@type":"NRID","@value":"9000413536468"},{"@type":"NRID","@value":"9000413528236"},{"@type":"NRID","@value":"9000412231423"},{"@type":"NRID","@value":"9000413850146"},{"@type":"NRID","@value":"9000399800496"},{"@type":"RESEARCHMAP","@value":"https://researchmap.jp/read0140726"}],"foaf:name":[{"@value":"Masayuki Yamamoto"}]},{"@id":"https://cir.nii.ac.jp/crid/1380847869282367620","@type":"Researcher","foaf:name":[{"@value":"John D. Hayes"}]}],"publication":{"publicationIdentifier":[{"@type":"PISSN","@value":"0041008X"}],"prism:publicationName":[{"@value":"Toxicology and Applied Pharmacology"}],"dc:publisher":[{"@value":"Elsevier BV"}],"prism:publicationDate":"2009-06","prism:volume":"237","prism:number":"3","prism:startingPage":"267","prism:endingPage":"280"},"reviewed":"false","dcterms:accessRights":"http://purl.org/coar/access_right/c_abf2","dc:rights":["https://www.elsevier.com/tdm/userlicense/1.0/"],"url":[{"@id":"https://api.elsevier.com/content/article/PII:S0041008X0900115X?httpAccept=text/xml"},{"@id":"https://api.elsevier.com/content/article/PII:S0041008X0900115X?httpAccept=text/plain"}],"createdAt":"2009-03-21","modifiedAt":"2021-10-03","foaf:topic":[{"@id":"https://cir.nii.ac.jp/all?q=INDUCIBLE%20EXPRESSION","dc:title":"INDUCIBLE EXPRESSION"},{"@id":"https://cir.nii.ac.jp/all?q=Glutathione%20S-transferases","dc:title":"Glutathione S-transferases"},{"@id":"https://cir.nii.ac.jp/all?q=Male","dc:title":"Male"},{"@id":"https://cir.nii.ac.jp/all?q=Free%20Radicals","dc:title":"Free Radicals"},{"@id":"https://cir.nii.ac.jp/all?q=NF-E2-Related%20Factor%202","dc:title":"NF-E2-Related Factor 2"},{"@id":"https://cir.nii.ac.jp/all?q=Menadione","dc:title":"Menadione"},{"@id":"https://cir.nii.ac.jp/all?q=DEFICIENT%20MICE","dc:title":"DEFICIENT MICE"},{"@id":"https://cir.nii.ac.jp/all?q=Xenobiotics","dc:title":"Xenobiotics"},{"@id":"https://cir.nii.ac.jp/all?q=Mice","dc:title":"Mice"},{"@id":"https://cir.nii.ac.jp/all?q=Isothiocyanates","dc:title":"Isothiocyanates"},{"@id":"https://cir.nii.ac.jp/all?q=ACETAMINOPHEN%20HEPATOTOXICITY","dc:title":"ACETAMINOPHEN HEPATOTOXICITY"},{"@id":"https://cir.nii.ac.jp/all?q=Animals","dc:title":"Animals"},{"@id":"https://cir.nii.ac.jp/all?q=OXIDATIVE%20STRESS","dc:title":"OXIDATIVE STRESS"},{"@id":"https://cir.nii.ac.jp/all?q=Acrolein","dc:title":"Acrolein"},{"@id":"https://cir.nii.ac.jp/all?q=Cells,%20Cultured","dc:title":"Cells, Cultured"},{"@id":"https://cir.nii.ac.jp/all?q=GENE-EXPRESSION","dc:title":"GENE-EXPRESSION"},{"@id":"https://cir.nii.ac.jp/all?q=DRUG-RESISTANCE","dc:title":"DRUG-RESISTANCE"},{"@id":"https://cir.nii.ac.jp/all?q=Mice,%20Knockout","dc:title":"Mice, Knockout"},{"@id":"https://cir.nii.ac.jp/all?q=500","dc:title":"500"},{"@id":"https://cir.nii.ac.jp/all?q=Fibroblasts","dc:title":"Fibroblasts"},{"@id":"https://cir.nii.ac.jp/all?q=Adaptation,%20Physiological","dc:title":"Adaptation, Physiological"},{"@id":"https://cir.nii.ac.jp/all?q=Glutathione","dc:title":"Glutathione"},{"@id":"https://cir.nii.ac.jp/all?q=Peroxides","dc:title":"Peroxides"},{"@id":"https://cir.nii.ac.jp/all?q=Mice,%20Inbred%20C57BL","dc:title":"Mice, Inbred C57BL"},{"@id":"https://cir.nii.ac.jp/all?q=Cancer%20chemoprevention","dc:title":"Cancer chemoprevention"},{"@id":"https://cir.nii.ac.jp/all?q=Sulfoxides","dc:title":"Sulfoxides"},{"@id":"https://cir.nii.ac.jp/all?q=Chlorambucil","dc:title":"Chlorambucil"},{"@id":"https://cir.nii.ac.jp/all?q=REACTIVE%20OXYGEN","dc:title":"REACTIVE OXYGEN"},{"@id":"https://cir.nii.ac.jp/all?q=OLIGONUCLEOTIDE%20MICROARRAY","dc:title":"OLIGONUCLEOTIDE MICROARRAY"},{"@id":"https://cir.nii.ac.jp/all?q=Oxidation-Reduction","dc:title":"Oxidation-Reduction"},{"@id":"https://cir.nii.ac.jp/all?q=CHEMOPREVENTIVE%20ISOTHIOCYANATE","dc:title":"CHEMOPREVENTIVE ISOTHIOCYANATE"},{"@id":"https://cir.nii.ac.jp/all?q=Thiocyanates","dc:title":"Thiocyanates"}],"project":[{"@id":"https://cir.nii.ac.jp/crid/1040000782028107904","@type":"Project","projectIdentifier":[{"@type":"KAKEN","@value":"20117010"},{"@type":"JGN","@value":"JP20117010"},{"@type":"URI","@value":"https://kaken.nii.ac.jp/grant/KAKENHI-PLANNED-20117010/"}],"notation":[{"@language":"ja","@value":"活性酸素シグナルの転写制御機構の解明"},{"@language":"en","@value":"Transcriptional regulation by reactive oxygen species"}]},{"@id":"https://cir.nii.ac.jp/crid/1040282257405851904","@type":"Project","projectIdentifier":[{"@type":"KAKEN","@value":"17013017"},{"@type":"JGN","@value":"JP17013017"},{"@type":"URI","@value":"https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-17013017/"}],"notation":[{"@language":"ja","@value":"細胞の癌化とその抑制における転写因子の役割"},{"@language":"en","@value":"Roles of transcription factors for carcinogenesis and carcinogenesisdefense"}]}],"relatedProduct":[{"@id":"https://cir.nii.ac.jp/crid/1050001202616215168","@type":"Article","resourceType":"学術雑誌論文(journal article)","relationType":["references"],"jpcoar:relatedTitle":[{"@language":"en","@value":"Ultraviolet A Irradiation Induces NF-E2-Related Factor 2 Activation in Dermal Fibroblasts: Protective Role in UVA-Induced Apoptosis"}]},{"@id":"https://cir.nii.ac.jp/crid/1050282677597219712","@type":"Article","resourceType":"学術雑誌論文(journal article)","relationType":["isReferencedBy"],"jpcoar:relatedTitle":[{"@language":"en","@value":"Conservation of the Keap1-Nrf2 System: An Evolutionary Journey through Stressful Space and Time"}]},{"@id":"https://cir.nii.ac.jp/crid/1360002218469806080","@type":"Article","resourceType":"学術雑誌論文(journal article)","relationType":["isReferencedBy"],"jpcoar:relatedTitle":[{"@value":"Genetic Evidence of an Evolutionarily Conserved Role for Nrf2 in the Protection against Oxidative 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Purification and characterization of glutathione <i>S</i>-transferase Ya1Ya1"}]},{"@id":"https://cir.nii.ac.jp/crid/1361137044229986304","@type":"Article","relationType":["references"],"jpcoar:relatedTitle":[{"@value":"Nrf2 and p53 cooperatively protect against BBN-induced urinary bladder carcinogenesis"}]},{"@id":"https://cir.nii.ac.jp/crid/1361137045422121344","@type":"Article","relationType":["references"],"jpcoar:relatedTitle":[{"@value":"Gene expression profiles induced by cancer chemopreventive isothiocyanate sulforaphane in the liver of C57BL/6J mice and C57BL/6J/Nrf2 (−/−) mice"}]},{"@id":"https://cir.nii.ac.jp/crid/1361418518558531456","@type":"Article","relationType":["references"],"jpcoar:relatedTitle":[{"@value":"Attenuation of UVB-Induced Sunburn Reaction and Oxidative DNA Damage with no Alterations in UVB-Induced Skin Carcinogenesis in Nrf2 Gene-Deficient 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