Preferential expression of antioxidant response element mediated gene expression in astrocytes

Citation
Th. Murphy et al., Preferential expression of antioxidant response element mediated gene expression in astrocytes, J NEUROCHEM, 76(6), 2001, pp. 1670-1678
Citations number
51
Categorie Soggetti
Neurosciences & Behavoir
Journal title
JOURNAL OF NEUROCHEMISTRY
ISSN journal
00223042 → ACNP
Volume
76
Issue
6
Year of publication
2001
Pages
1670 - 1678
Database
ISI
SICI code
0022-3042(200103)76:6<1670:PEOARE>2.0.ZU;2-S
Abstract
Transcriptional control of target genes by antioxidant/electrophile respons e elements has been well described in peripheral tissues. Genes that are re gulated by this mechanism include the antioxidant enzymes NAD(P)H:quinone o xidoreductase, gamma -glutamyl cystine synthetase and glutathione-S-transfe rase. Antioxidant/electrophile response elements within a gene's promoter c onfer induction by low-molecular-weight electrophilic compounds such as ter t-butylhydroquinone and dimethyl fumarate. We have now examined the ability of antioxidant/electrophile response elements to elicit gene expression in neurons and astrocytes in both brain slices and primary cultures using tra nsient transfection of promoter reporter constructs. Our results using a he at-stable human placental alkaline phosphatase reporter indicate that antio xidant/electrophile response element mediated gene expression is largely re stricted to astrocyte cell populations. Placental alkaline phosphatase expr ession was significantly elevated in astrocytes treated with the antioxidan t/electrophile response element inducer dimethyl fumarate. Mutant construct s lacking a functional antioxidant/electrophile response element abolished all placental alkaline phosphatase expression in astrocytes. We suggest tha t astrocytic metabolic processes that normally aid and/or protect neurons m ay be controlled via this inducible system.