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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
21
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pubmed:dateCreated |
2000-6-30
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pubmed:abstractText |
Electrophiles and reactive oxygen species have been implicated in the pathogenesis of many diseases. Transcription factor Nrf2 was recently identified as a general regulator of one defense mechanism against such havoc. Nrf2 regulates the inducible expression of a group of detoxication enzymes, such as glutathione S-transferase and NAD(P)H:quinone oxidoreductase, via antioxidant response elements. Using peritoneal macrophages from Nrf2-deficient mice, we show here that Nrf2 also controls the expression of a group of electrophile- and oxidative stress-inducible proteins and activities, which includes heme oxygenase-1, A170, peroxiredoxin MSP23, and cystine membrane transport (system x(c)(-)) activity. The response to electrophilic and reactive oxygen species-producing agents was profoundly impaired in Nrf2-deficient cells. The lack of induction of system x(c)(-) activity resulted in the minimum level of intracellular glutathione, and Nrf2-deficient cells were more sensitive to toxic electrophiles. Several stress agents induced the DNA binding activity of Nrf2 in the nucleus without increasing its mRNA level. Thus Nrf2 regulates a wide-ranging metabolic response to oxidative stress.
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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/Adaptor Proteins, Signal Transducing,
http://linkedlifedata.com/resource/pubmed/chemical/DNA-Binding Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Heat-Shock Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Heme Oxygenase (Decyclizing),
http://linkedlifedata.com/resource/pubmed/chemical/Heme Oxygenase-1,
http://linkedlifedata.com/resource/pubmed/chemical/Hmox1 protein, mouse,
http://linkedlifedata.com/resource/pubmed/chemical/Membrane Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/NF-E2-Related Factor 2,
http://linkedlifedata.com/resource/pubmed/chemical/Nfe2l2 protein, mouse,
http://linkedlifedata.com/resource/pubmed/chemical/Oxidants,
http://linkedlifedata.com/resource/pubmed/chemical/Peroxidases,
http://linkedlifedata.com/resource/pubmed/chemical/Peroxiredoxins,
http://linkedlifedata.com/resource/pubmed/chemical/Prdx1 protein, mouse,
http://linkedlifedata.com/resource/pubmed/chemical/RNA, Messenger,
http://linkedlifedata.com/resource/pubmed/chemical/Reactive Oxygen Species,
http://linkedlifedata.com/resource/pubmed/chemical/Sqstm1 protein, mouse,
http://linkedlifedata.com/resource/pubmed/chemical/Trans-Activators
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pubmed:status |
MEDLINE
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pubmed:month |
May
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pubmed:issn |
0021-9258
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pubmed:author |
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pubmed:issnType |
Print
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pubmed:day |
26
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pubmed:volume |
275
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
16023-9
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pubmed:dateRevised |
2007-11-15
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pubmed:meshHeading |
pubmed-meshheading:10821856-Adaptor Proteins, Signal Transducing,
pubmed-meshheading:10821856-Animals,
pubmed-meshheading:10821856-DNA-Binding Proteins,
pubmed-meshheading:10821856-Female,
pubmed-meshheading:10821856-Gene Expression Regulation,
pubmed-meshheading:10821856-Heat-Shock Proteins,
pubmed-meshheading:10821856-Heme Oxygenase (Decyclizing),
pubmed-meshheading:10821856-Heme Oxygenase-1,
pubmed-meshheading:10821856-Macrophages, Peritoneal,
pubmed-meshheading:10821856-Membrane Proteins,
pubmed-meshheading:10821856-Mice,
pubmed-meshheading:10821856-Mice, Inbred Strains,
pubmed-meshheading:10821856-Mice, Knockout,
pubmed-meshheading:10821856-NF-E2-Related Factor 2,
pubmed-meshheading:10821856-Oxidants,
pubmed-meshheading:10821856-Oxidative Stress,
pubmed-meshheading:10821856-Peroxidases,
pubmed-meshheading:10821856-Peroxiredoxins,
pubmed-meshheading:10821856-RNA, Messenger,
pubmed-meshheading:10821856-Reactive Oxygen Species,
pubmed-meshheading:10821856-Trans-Activators
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pubmed:year |
2000
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pubmed:articleTitle |
Transcription factor Nrf2 coordinately regulates a group of oxidative stress-inducible genes in macrophages.
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pubmed:affiliation |
Institute of Basic Medical Sciences and Center for Tsukuba Advanced Research Alliance, University of Tsukuba, 1-1-1 Tennoudai, Tsukuba 305-8577, Japan.
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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