Linked Life Data

14522084

Source:http://linkedlifedata.com/resource/pubmed/id/14522084

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
1-3
pubmed:dateCreated
2003-10-2
pubmed:abstractText
The antioxidant responsive element (ARE) plays an important role in the gene expression of phase II detoxification enzymes, such as NAD(P)H:quinone oxidoreductase 1 (NQO1), and NF-E2-related factor2 (Nrf2) is the transcription factor for the ARE-driven genes. Interestingly, estrogen receptor (ER) was reported to increase NQO1 gene expression through the ARE. In this study, we investigated the role of ER and Nrf2 in ARE activation using IMR-32 cells and mouse primary astrocytes. Among tested estrogen-related compounds, only catechol estrogens (i.e. 4-hydroxyestradiol) activated the ARE. Since 4-hydroxyestradiol-induced ARE activation was not inhibited by either 17beta-estradiol or tamoxifen, and overexpression of ER-alpha decreased 4-hydroxyestradiol-induced ARE activation, ARE activation by catechol estrogen was independent of ER. Nrf2, however, was very important in the 4-hydroxyestradiol-induced ARE activation. 4-Hydroxyestradiol did not activate the ARE in Nrf2 knockout (-/-) primary astrocytes, but did activate the ARE when Nrf2 was transfected into Nrf2-/- astrocytes. In addition, dominant negative Nrf2 completely blocked 4-hydroxyestradiol-induced ARE activation in Nrf2+/+ astrocytes, and only 4-hydroxyestradiol induced Nrf2 nuclear translocation in IMR-32 cells. A selective phosphatidylinositol 3-kinase (PI3-kinase) inhibitor (LY294002) blocked 4-hydroxyestradiol-induced Nrf2 nuclear translocation and NQO1 activity induction in IMR-32 cells. Taken together, these observations suggest that 4-hydroxyestradiol activates the ARE by a PI3-kinase-Nrf2 dependent mechanism, not involving ER.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
http://linkedlifedata.com/resource/pubmed/chemical/Antioxidants, http://linkedlifedata.com/resource/pubmed/chemical/DNA-Binding Proteins, http://linkedlifedata.com/resource/pubmed/chemical/Estrogen Receptor alpha, http://linkedlifedata.com/resource/pubmed/chemical/Estrogens, Catechol, http://linkedlifedata.com/resource/pubmed/chemical/NAD(P)H Dehydrogenase (Quinone), 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/NQO1 protein, human, http://linkedlifedata.com/resource/pubmed/chemical/Nfe2l2 protein, mouse, http://linkedlifedata.com/resource/pubmed/chemical/Phosphatidylinositol 3-Kinases, http://linkedlifedata.com/resource/pubmed/chemical/Receptors, Estrogen, http://linkedlifedata.com/resource/pubmed/chemical/Trans-Activators
pubmed:status
MEDLINE
pubmed:month
Oct
pubmed:issn
0006-3002
pubmed:author
pubmed:issnType
Print
pubmed:day
1
pubmed:volume
1629
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
92-101
pubmed:dateRevised
2010-11-18
pubmed:meshHeading
pubmed:year
2003
pubmed:articleTitle
Nrf2, not the estrogen receptor, mediates catechol estrogen-induced activation of the antioxidant responsive element.
pubmed:affiliation
School of Pharmacy, University of Wisconsin, 777 Highland Avenue, Madison, WI 53705, USA.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S., Research Support, Non-U.S. Gov't