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Preferential expression of antioxidant response element mediated gene expression in astrocytes
Author(s) -
Murphy T. H.,
Yu J.,
Ng R.,
Johnson D. A.,
Shen H.,
Honey C. R.,
Johnson J. A.
Publication year - 2001
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1046/j.1471-4159.2001.00157.x
Subject(s) - antioxidant , gene expression , response element , biology , glutathione , biochemistry , regulation of gene expression , alkaline phosphatase , microbiology and biotechnology , enzyme , gene , promoter
Transcriptional control of target genes by antioxidant/electrophile response elements has been well described in peripheral tissues. Genes that are regulated by this mechanism include the antioxidant enzymes NAD(P)H:quinone oxidoreductase, γ‐glutamyl cystine synthetase and glutathione‐ S ‐transferase. Antioxidant/electrophile response elements within a gene's promoter confer induction by low‐molecular‐weight electrophilic compounds such as tert ‐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 transient transfection of promoter reporter constructs. Our results using a heat‐stable human placental alkaline phosphatase reporter indicate that antioxidant/electrophile response element mediated gene expression is largely restricted to astrocyte cell populations. Placental alkaline phosphatase expression was significantly elevated in astrocytes treated with the antioxidant/electrophile response element inducer dimethyl fumarate. Mutant constructs lacking a functional antioxidant/electrophile response element abolished all placental alkaline phosphatase expression in astrocytes. We suggest that astrocytic metabolic processes that normally aid and/or protect neurons may be controlled via this inducible system.