Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
6
pubmed:dateCreated
2006-9-1
pubmed:abstractText
The transcription factor, nuclear factor E2 (erythroid-derived 2)-related factor 2 (Nrf2), is essential for the induction of a battery of phase II detoxification genes through the antioxidant response element (ARE) that lies in their promoter region. Genes driven by the ARE are up-regulated in response to various stressors of the cellular environment. These genetic changes to the cellular reducing potential may reflect an intrinsic damage response to harmful toxicants. Analysis of transgenic reporter mice following kainate injection revealed selective ARE activation within the damaged hippocampus. Further, 2 x 2 microarray analyses comparing Nrf2 knockout versus wild-type hippocampi unmasked gene changes associated with ion movement and myelination, in addition to alterations to detoxification-related genes. Nrf2 knockout mice were more sensitive to kainate toxicity, as evidenced by elevated seizure severity, seizure duration, hippocampal neuron damage and mortality. Knockout mice injected with kainate displayed altered glial fibrillary acidic protein immunoreactivity and increased microglial infiltration. The wild-type to knockout damage differential was not dependent on the peripheral metabolism of the excitotoxin, was well correlated with increased seizure susceptibility, and was therefore not necessarily the neuroprotective effects of Nrf2. These results combine to support a role for Nrf2 in the neural cell defense response of the adult brain.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Sep
pubmed:issn
0022-3042
pubmed:author
pubmed:issnType
Print
pubmed:volume
98
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1852-65
pubmed:dateRevised
2007-11-14
pubmed:meshHeading
pubmed-meshheading:16945104-Animals, pubmed-meshheading:16945104-Antioxidants, pubmed-meshheading:16945104-Disease Susceptibility, pubmed-meshheading:16945104-Excitatory Amino Acid Agonists, pubmed-meshheading:16945104-Female, pubmed-meshheading:16945104-Glial Fibrillary Acidic Protein, pubmed-meshheading:16945104-Hippocampus, pubmed-meshheading:16945104-Kainic Acid, pubmed-meshheading:16945104-Male, pubmed-meshheading:16945104-Mice, pubmed-meshheading:16945104-Mice, Knockout, pubmed-meshheading:16945104-Mice, Transgenic, pubmed-meshheading:16945104-Microglia, pubmed-meshheading:16945104-NF-E2-Related Factor 2, pubmed-meshheading:16945104-Nerve Degeneration, pubmed-meshheading:16945104-Neurons, pubmed-meshheading:16945104-Neurotoxins, pubmed-meshheading:16945104-Oligonucleotide Array Sequence Analysis, pubmed-meshheading:16945104-Response Elements, pubmed-meshheading:16945104-Seizures
pubmed:year
2006
pubmed:articleTitle
Neuronal sensitivity to kainic acid is dependent on the Nrf2-mediated actions of the antioxidant response element.
pubmed:affiliation
University of Wisconsin, Madison, WI, USA.
pubmed:publicationType
Journal Article, Research Support, N.I.H., Extramural