PMID- 14522084
OWN - NLM
STAT- MEDLINE
DCOM- 20031107
LR  - 20220317
IS  - 0006-3002 (Print)
IS  - 0006-3002 (Linking)
VI  - 1629
IP  - 1-3
DP  - 2003 Oct 1
TI  - Nrf2, not the estrogen receptor, mediates catechol estrogen-induced activation of 
      the antioxidant responsive element.
PG  - 92-101
AB  - 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.
FAU - Lee, Jong-Min
AU  - Lee JM
AD  - School of Pharmacy, University of Wisconsin, 777 Highland Avenue, Madison, WI 
      53705, USA.
FAU - Anderson, Peter C
AU  - Anderson PC
FAU - Padgitt, Janette K
AU  - Padgitt JK
FAU - Hanson, Janean M
AU  - Hanson JM
FAU - Waters, Christopher M
AU  - Waters CM
FAU - Johnson, Jeffrey A
AU  - Johnson JA
LA  - eng
GR  - ES08089/ES/NIEHS NIH HHS/United States
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - Netherlands
TA  - Biochim Biophys Acta
JT  - Biochimica et biophysica acta
JID - 0217513
RN  - 0 (Antioxidants)
RN  - 0 (DNA-Binding Proteins)
RN  - 0 (Estrogen Receptor alpha)
RN  - 0 (Estrogens, Catechol)
RN  - 0 (NF-E2-Related Factor 2)
RN  - 0 (NFE2L2 protein, human)
RN  - 0 (Nfe2l2 protein, mouse)
RN  - 0 (Receptors, Estrogen)
RN  - 0 (Trans-Activators)
RN  - EC 1.6.5.2 (NAD(P)H Dehydrogenase (Quinone))
RN  - EC 1.6.5.2 (NQO1 protein, human)
RN  - EC 2.7.1.- (Phosphatidylinositol 3-Kinases)
SB  - IM
MH  - Animals
MH  - Antioxidants/*metabolism
MH  - DNA-Binding Proteins/*physiology
MH  - Estrogen Receptor alpha
MH  - Estrogens, Catechol/physiology
MH  - Humans
MH  - Mice
MH  - NAD(P)H Dehydrogenase (Quinone)/metabolism
MH  - NF-E2-Related Factor 2
MH  - Oxidative Stress
MH  - Phosphatidylinositol 3-Kinases/metabolism
MH  - Receptors, Estrogen/physiology
MH  - Response Elements
MH  - Trans-Activators/*physiology
MH  - Transfection
MH  - Tumor Cells, Cultured
EDAT- 2003/10/03 05:00
MHDA- 2003/11/08 05:00
CRDT- 2003/10/03 05:00
PHST- 2003/10/03 05:00 [pubmed]
PHST- 2003/11/08 05:00 [medline]
PHST- 2003/10/03 05:00 [entrez]
AID - S0167478103001805 [pii]
AID - 10.1016/j.bbaexp.2003.08.006 [doi]
PST - ppublish
SO  - Biochim Biophys Acta. 2003 Oct 1;1629(1-3):92-101. doi: 
      10.1016/j.bbaexp.2003.08.006.