Source:http://linkedlifedata.com/resource/pubmed/id/12556532
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| Predicate | Object |
|---|---|
| rdf:type | |
| lifeskim:mentions | |
| pubmed:issue |
14
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| pubmed:dateCreated |
2003-3-31
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| pubmed:abstractText |
The antioxidant responsive element (ARE) mediates transcriptional regulation of phase II detoxification enzymes and antioxidant proteins such as NAD(P)H:quinone oxidoreductase (NQO1), glutathione S-transferases, and glutamate-cysteine ligase. In this study, we demonstrate that NF-E2-related factor-2 (Nrf2) plays a major role in transcriptional activation of ARE-driven genes and identify Nrf2-dependent genes by oligonucleotide microarray analysis using primary cortical astrocytes from Nrf2(+/+) and Nrf2(-/-) mice. Nrf2(-/-) astrocytes had decreased basal NQO1 activity and no induction by tert-butylhydroquinone compared with Nrf2(+/+) astrocytes. Similarly, both basal and induced levels of human NQO1-ARE-luciferase expression in Nrf2(-/-) astrocytes were significantly lower than in Nrf2(+/+) astrocytes. Furthermore, human NQO1-ARE-luciferase expression in Nrf2(-/-) astrocytes was restored by overexpression of Nrf2, whereas ARE activation in Nrf2(+/+) astrocytes was completely blocked by dominant-negative Nrf2. In addition, we observed that Nrf2-dependent genes protected primary astrocytes from H(2)O(2)- or platelet-activating factor-induced apoptosis. In support of these observations, we identified Nrf2-dependent genes encoding detoxification enzymes, glutathione-related proteins, antioxidant proteins, NADPH-producing enzymes, and anti-inflammatory genes using oligonucleotide microarrays. Proteins within these functional categories are vital to the maintenance and responsiveness of a cell defense system, suggesting that an orchestrated change in gene expression via Nrf2 and the ARE gives a synergistic protective effect against oxidative stress.
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| pubmed:grant | |
| pubmed:language |
eng
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| pubmed:journal | |
| pubmed:citationSubset |
IM
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| pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/2-tert-butylhydroquinone,
http://linkedlifedata.com/resource/pubmed/chemical/Antioxidants,
http://linkedlifedata.com/resource/pubmed/chemical/Cytotoxins,
http://linkedlifedata.com/resource/pubmed/chemical/DNA-Binding Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Hydrogen Peroxide,
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, mouse,
http://linkedlifedata.com/resource/pubmed/chemical/Oligonucleotides,
http://linkedlifedata.com/resource/pubmed/chemical/Oxidants,
http://linkedlifedata.com/resource/pubmed/chemical/Platelet Activating Factor,
http://linkedlifedata.com/resource/pubmed/chemical/Trans-Activators
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| pubmed:status |
MEDLINE
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| pubmed:month |
Apr
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| pubmed:issn |
0021-9258
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| pubmed:author | |
| pubmed:issnType |
Print
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| pubmed:day |
4
|
| pubmed:volume |
278
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| pubmed:owner |
NLM
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| pubmed:authorsComplete |
Y
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| pubmed:pagination |
12029-38
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| pubmed:dateRevised |
2007-11-14
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| pubmed:meshHeading |
pubmed-meshheading:12556532-Animals,
pubmed-meshheading:12556532-Antioxidants,
pubmed-meshheading:12556532-Astrocytes,
pubmed-meshheading:12556532-Cells, Cultured,
pubmed-meshheading:12556532-Cerebral Cortex,
pubmed-meshheading:12556532-Cytotoxins,
pubmed-meshheading:12556532-DNA-Binding Proteins,
pubmed-meshheading:12556532-Female,
pubmed-meshheading:12556532-Hydrogen Peroxide,
pubmed-meshheading:12556532-Hydroquinones,
pubmed-meshheading:12556532-Male,
pubmed-meshheading:12556532-Mice,
pubmed-meshheading:12556532-Mice, Knockout,
pubmed-meshheading:12556532-NF-E2-Related Factor 2,
pubmed-meshheading:12556532-Oligonucleotide Array Sequence Analysis,
pubmed-meshheading:12556532-Oligonucleotides,
pubmed-meshheading:12556532-Oxidants,
pubmed-meshheading:12556532-Oxidative Stress,
pubmed-meshheading:12556532-Platelet Activating Factor,
pubmed-meshheading:12556532-Trans-Activators
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| pubmed:year |
2003
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| pubmed:articleTitle |
Identification of the NF-E2-related factor-2-dependent genes conferring protection against oxidative stress in primary cortical astrocytes using oligonucleotide microarray analysis.
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| pubmed:affiliation |
School of Pharmacy, Molecular and Environmental Toxicology Center, University of Wisconsin, Madison, Wisconsin 53705, USA.
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| pubmed:publicationType |
Journal Article,
Research Support, U.S. Gov't, P.H.S.,
Research Support, Non-U.S. Gov't
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