Linked Life Data

11342101

Source:http://linkedlifedata.com/resource/pubmed/id/11342101

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
2
pubmed:dateCreated
2001-5-8
pubmed:abstractText
Gamma-glutamylcysteinylglycine or glutathione (GSH) performs important protective functions in the cell through maintenance of the intracellular redox balance and elimination of xenobiotics and free radicals. The production of GSH involves a number of enzymes and enzyme subunits offering multiple opportunities for regulation. Two members of the CNC subfamily of bZIP transcription factors (TCF11/Nrf1 and Nrf2) have been implicated in the regulation of detoxification enzymes and the oxidative stress response. Here we investigate the potential role of one of these factors, TCF11/Nrf1, in the regulation of GSH levels in the cell and particularly its influence on the expression of one of the enzymatic components necessary for the synthesis of GSH, the heavy subunit of gamma-glutamylcysteine synthetase (GCS(h)). Using overexpression of the transcription factor in COS-1 cells we show that TCF11/Nrf1 stimulates GSH accumulation. Using co-transfection with reporter constructs where reporter expression is driven through the GCS(h) promoter we show that this increase may be mediated in part by induced expression of the GCS(h) gene by TCF11/Nrf1. We further show that a distal portion of the promoter including two antioxidant-response elements (AREs) predominantly mediates the TCF11/Nrf1 transactivation and an electromobility shift assay showed that just one of these AREs specifically binds TCF11/Nrf1 as heterodimers with small Maf proteins. We suggest that TCF11/Nrf1 can operate through a subset of AREs to modulate the expression of GCS(h) together with other components of the pathway and in this way play a role in regulating cellular glutathione levels.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jan
pubmed:issn
0006-3002
pubmed:author
pubmed:issnType
Print
pubmed:day
26
pubmed:volume
1517
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
212-9
pubmed:dateRevised
2008-11-21
pubmed:meshHeading
pubmed:year
2001
pubmed:articleTitle
TCF11/Nrf1 overexpression increases the intracellular glutathione level and can transactivate the gamma-glutamylcysteine synthetase (GCS) heavy subunit promoter.
pubmed:affiliation
Institute for Nutrition Research, University of Oslo, Oslo, Norway.
pubmed:publicationType
Journal Article