Linked Life Data

18204073

Source:http://linkedlifedata.com/resource/pubmed/id/18204073

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
4
pubmed:dateCreated
2008-4-2
pubmed:abstractText
A major component of the anticarcinogenic activity of the dietary chemopreventive agent sulforaphane (SFN) is attributed to its ability to induce expression of phase II detoxification genes containing the antioxidant response element (ARE) within their promoters. Because SFN is a reactive electrophile--readily forming conjugates with glutathione (GSH)--we asked whether expression of glutathione S-transferase (GST) P1-1 and the GSH conjugate efflux pump, multidrug resistance or resistance-associated protein (MRP) 1, would significantly modify the cellular response to SFN exposure. This was investigated using GST- and MRP1-poor parental MCF7 cells and transgenic derivatives expressing GSTP1-1 and/or MRP1. Compared with parental cells, expression of GSTP1-1 alone enhanced the rate of intracellular accumulation of SFN and its glutathione conjugate, SFN-SG--an effect that was associated with increased ARE-containing reporter gene induction. Expression of MRP1 greatly reduced SFN/SFN-SG accumulation and resulted in significant attenuation of SFN-mediated induction of ARE-containing reporter and endogenous gene expression. Coexpression of GSTP1-1 with MRP1 further reduced the level of induction. Depletion of GSH prior to SFN treatment or the substitution of tert-butylhydroquinone for SFN abolished the effects of MRP1/GSTP1-1 on ARE-containing gene induction-indicating that these effects are GSH dependent. Lastly, analysis of NF-E2-related factor 2 (Nrf2)--a transcription factor operating via binding to the ARE--showed that the increased levels of Nrf2 following SFN treatment were considerably less sustained in MRP1-expressing, especially those coexpressing GSTP1-1, than in MRP1-poor cells. These results suggest that the regulating effects of MRP1 and GSTP1-1 expression on SFN-dependent induction of phase II genes are ultimately mediated by altering nuclear Nrf2 levels.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Apr
pubmed:issn
1460-2180
pubmed:author
pubmed:issnType
Electronic
pubmed:volume
29
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
807-15
pubmed:dateRevised
2008-11-21
pubmed:meshHeading
pubmed:year
2008
pubmed:articleTitle
Expression of MRP1 and GSTP1-1 modulate the acute cellular response to treatment with the chemopreventive isothiocyanate, sulforaphane.
pubmed:affiliation
Department of Biochemistry, Wake Forest University School of Medicine, Medical Center Boulevard, Winston-Salem, NC 27157, USA.
pubmed:publicationType
Journal Article, Research Support, N.I.H., Extramural