Preferential expression of antioxidant response element mediated gene expression in astrocytes
| Autor: | T H, Murphy, J, Yu, R, Ng, D A, Johnson, H, Shen, C R, Honey, J A, Johnson |
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| Rok vydání: | 2001 |
| Předmět: |
Dimethyl Fumarate
Glutamate-Cysteine Ligase Recombinant Fusion Proteins Molecular Sequence Data In Vitro Techniques Transfection Antioxidants Gene Expression Regulation Enzymologic Neuroblastoma Fumarates Genes Reporter Animals Humans Quinone Reductases Promoter Regions Genetic Cells Cultured Glutathione Transferase Cerebral Cortex Hybridomas Base Sequence Glioma Biolistics Hydroquinones Rats Astrocytes Neuroglia |
| Zdroj: | Journal of neurochemistry. 76(6) |
| ISSN: | 0022-3042 |
| Popis: | 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, gamma-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. |
| Databáze: | OpenAIRE |
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