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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
1
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pubmed:dateCreated |
2004-10-19
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pubmed:abstractText |
Nrf-2 is a redox-sensitive transcription factor that is activated by an oxidative signal in the cytoplasm but has a critical cysteine that must be reduced to bind to DNA in the nucleus. The glutathione (GSH) and thioredoxin (TRX) systems have overlapping functions in thiol/disulfide redox control in both the cytoplasm and the nucleus, and it is unclear whether these are redundant or have unique functions in control of Nrf-2-dependent signaling. To test whether GSH and Trx-1 have distinct functions in Nrf-2 signaling, we selectively modified GSH by metabolic manipulation and selectively modified Trx-1 expression by transient transfection. Cytoplasmic activation of Nrf-2 was measured by its nuclear translocation and nuclear activity of Nrf-2 was measured by expression of a luciferase reporter construct containing an ARE4 from glutamate cysteine ligase. Results showed that tert-butylhydroquinone (TBHQ), a transcriptional activator that functions through Nrf-2/ARE, promoted Nrf-2 nuclear translocation by a type I (thiylation) redox switch which was regulated by GSH not by Trx-1. In contrast, the ARE reporter was principally controlled by nuclear-targeted Trx-1 and not by GSH. The data show that the GSH and TRX systems have unique, compartmented functions in the control of transcriptional regulation by Nrf-2/ARE.
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pubmed:grant |
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pubmed:commentsCorrections |
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/2-tert-butylhydroquinone,
http://linkedlifedata.com/resource/pubmed/chemical/Acetylcysteine,
http://linkedlifedata.com/resource/pubmed/chemical/Buthionine Sulfoximine,
http://linkedlifedata.com/resource/pubmed/chemical/DNA,
http://linkedlifedata.com/resource/pubmed/chemical/DNA-Binding Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Glutathione,
http://linkedlifedata.com/resource/pubmed/chemical/Hydroquinones,
http://linkedlifedata.com/resource/pubmed/chemical/NF-E2-Related Factor 2,
http://linkedlifedata.com/resource/pubmed/chemical/NFE2L2 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/TXN protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Thioredoxins,
http://linkedlifedata.com/resource/pubmed/chemical/Trans-Activators
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pubmed:status |
MEDLINE
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pubmed:month |
Nov
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pubmed:issn |
1096-6080
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pubmed:author |
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pubmed:issnType |
Print
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pubmed:volume |
82
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
308-17
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pubmed:dateRevised |
2010-9-17
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pubmed:meshHeading |
pubmed-meshheading:15282410-Acetylcysteine,
pubmed-meshheading:15282410-Binding Sites,
pubmed-meshheading:15282410-Buthionine Sulfoximine,
pubmed-meshheading:15282410-Cell Nucleus,
pubmed-meshheading:15282410-DNA,
pubmed-meshheading:15282410-DNA-Binding Proteins,
pubmed-meshheading:15282410-Dose-Response Relationship, Drug,
pubmed-meshheading:15282410-Gene Expression Regulation,
pubmed-meshheading:15282410-Glutathione,
pubmed-meshheading:15282410-HeLa Cells,
pubmed-meshheading:15282410-Humans,
pubmed-meshheading:15282410-Hydroquinones,
pubmed-meshheading:15282410-NF-E2-Related Factor 2,
pubmed-meshheading:15282410-Oxidation-Reduction,
pubmed-meshheading:15282410-Signal Transduction,
pubmed-meshheading:15282410-Thioredoxins,
pubmed-meshheading:15282410-Trans-Activators,
pubmed-meshheading:15282410-Transfection
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pubmed:year |
2004
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pubmed:articleTitle |
Compartmentation of Nrf-2 redox control: regulation of cytoplasmic activation by glutathione and DNA binding by thioredoxin-1.
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pubmed:affiliation |
Department of Medicine and Biochemistry, Emory University School of Medicine, Atlanta, GA 30322, USA.
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pubmed:publicationType |
Journal Article,
Research Support, U.S. Gov't, P.H.S.
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