Linked Life Data

11098127

Source:http://linkedlifedata.com/resource/pubmed/id/11098127

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
3
pubmed:dateCreated
2000-12-11
pubmed:abstractText
The translocation of synaptic Zn(2+) from nerve terminals into selectively vulnerable neurons may contribute to the death of these neurons after global ischemia. We hypothesized that cellular Zn(2+) overload might be lethal for reasons similar to cellular Ca(2+) overload and tested the hypothesis that Zn(2+) neurotoxicity might be mediated by the activation of nitric oxide synthase. Although Zn(2+) (30-300microM) altered nitric oxide synthase activity in cerebellar extracts in solution, it did not affect nitric oxide synthase activity in cultured murine neocortical neurons. Cultured neurons exposed to 300-500microM Zn(2+) for 5min under depolarizing conditions developed widespread degeneration over the next 24h that was unaffected by the concurrent addition of the nitric oxide synthase inhibitor N(G)-nitro-L-arginine. Furthermore, Zn(2+) neurotoxicity was attenuated when nitric oxide synthase activity in the cultures was induced by exposure to cytokines, exogenous nitric oxide was added or nitric oxide production was pharmacologically enhanced. The unexpected protective effect of nitric oxide against Zn(2+) toxicity may be explained, at least in part, by reduction of toxic Zn(2+) entry. Exposure to nitric oxide donors reduced Ba(2+) current through high-voltage activated calcium channels, as well as K(+)-stimulated neuronal uptake of 45Ca(2+) or 65Zn(2+). The oxidizing agents thimerosal and 2,2'-dithiodipyridine also reduced K(+)-stimulated cellular 45Ca(2+) uptake, while akylation of thiols by pretreatment with N-ethylmaleimide blocked the reduction of 45Ca(2+) uptake by a nitric oxide donor.The results suggest that Zn(2+)-induced neuronal death is not mediated by the activation of nitric oxide synthase; rather, available nitric oxide may attenuate Zn(2+) neurotoxicity by reducing Zn(2+) entry through voltage-gated Ca(2+) channels, perhaps by oxidizing key thiol groups.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:issn
0306-4522
pubmed:author
pubmed:issnType
Print
pubmed:volume
100
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
651-61
pubmed:dateRevised
2007-11-14
pubmed:meshHeading
pubmed:year
2000
pubmed:articleTitle
Nitric oxide reduces Ca(2+) and Zn(2+) influx through voltage-gated Ca(2+) channels and reduces Zn(2+) neurotoxicity.
pubmed:affiliation
Center for the Study of Nervous System Injury and Department of Neurology, Washington University School of Medicine, St Louis, Missouri, USA.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S.