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Predicate | Object |
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rdf:type | |
lifeskim:mentions | |
pubmed:issue |
11 Suppl
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pubmed:dateCreated |
1990-12-20
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pubmed:abstractText |
The role of oxygen-derived free radicals, superoxide in particular, in the pathogenesis of neuronal cell death induced by glutamate was studied using cultured cortical neurons from transgenic mice overexpressing human copper-zinc-superoxide dismutase. Primary cortical neuron cultures were developed from 15-day-old fetuses of both transgenic mice and their normal littermates. Both human copper-zinc-superoxide dismutase and host mouse copper-zinc-superoxide dismutase activities in cultured neurons were identified by native gel electrophoresis followed by nitroblue tetrazolium staining. Cultured neurons grown for 10-12 days in vitro were exposed briefly to 0.5 mM glutamate for 5 minutes, followed by biochemical and morphological examinations at 2, 4, and 24 hours. Our data have demonstrated that glutamate neurotoxicity is significantly reduced in transgenic neurons at 2 and 4 hours following exposure to glutamate, as measured by the efflux of lactate dehydrogenase, the 3-O-methyl glucose space, and by phase-contrast and bright-field trypan blue staining. These data indicate that transgenic neurons containing twofold to threefold the normal amount of copper-zinc-superoxide dismutase activity as the result of expression of the human copper-zinc-superoxide dismutase transgene are protected against glutamate neurotoxicity in vitro. Our results suggest that oxidative stress, at least in part, plays an important role in the biochemical pathways amplifying N-methyl-D-aspartate receptor-mediated neurotoxicity.
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pubmed:grant | |
pubmed:language |
eng
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pubmed:journal | |
pubmed:citationSubset |
IM
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pubmed:chemical | |
pubmed:status |
MEDLINE
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pubmed:month |
Nov
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pubmed:issn |
0039-2499
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pubmed:author | |
pubmed:issnType |
Print
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pubmed:volume |
21
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
III80-2
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pubmed:dateRevised |
2007-11-14
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pubmed:meshHeading |
pubmed-meshheading:2237989-Animals,
pubmed-meshheading:2237989-Cell Survival,
pubmed-meshheading:2237989-Copper,
pubmed-meshheading:2237989-Gene Expression,
pubmed-meshheading:2237989-Glutamates,
pubmed-meshheading:2237989-Mice,
pubmed-meshheading:2237989-Mice, Transgenic,
pubmed-meshheading:2237989-Nervous System,
pubmed-meshheading:2237989-Neurons,
pubmed-meshheading:2237989-Superoxide Dismutase,
pubmed-meshheading:2237989-Zinc
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pubmed:year |
1990
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pubmed:articleTitle |
Reduced neurotoxicity in transgenic mice overexpressing human copper-zinc-superoxide dismutase.
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pubmed:affiliation |
Department of Neurosurgery, University of California, School of Medicine, San Francisco 94143.
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pubmed:publicationType |
Journal Article,
Research Support, U.S. Gov't, P.H.S.
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