Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
6
pubmed:dateCreated
2003-9-26
pubmed:abstractText
We have previously suggested that zinc-induced neuronal death may be mediated in part by inhibition of the glycolytic enzyme glyceraldehyde-3-phosphate dehydrogenase (GAPDH), secondary to depletion of the essential cosubstrate NAD+. Given convergent evidence implicating the NAD+-catabolizing enzyme, poly ADP ribosyl polymerase (PARP) in mediating ATP depletion and neuronal death after excitotoxic and ischemic insults, we tested the specific hypothesis that the neuronal death induced by exposure to toxic levels of extracellular zinc might be partly mediated by PARP. PARP was activated in cultured mouse cortical astrocytes after a toxic acute Zn2+ exposure (350 microm Zn2+ for 15 min), but not in cortical neurons or glia after exposure to a toxic chronic Zn2+ exposure (40 microm Zn2+ for 1-4 h), an exposure sufficient to deplete NAD+ and ATP levels. Furthermore, the neurotoxicity induced by acute, but not chronic, Zn2+ exposure was reduced in mixed neuronal-glial cultures prepared from mutant mice lacking the PARP gene. These data suggest PARP activation may contribute to more fulminant forms of Zn2+-induced neuronal death.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Sep
pubmed:issn
0953-816X
pubmed:author
pubmed:issnType
Print
pubmed:volume
18
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1402-9
pubmed:dateRevised
2007-11-15
pubmed:meshHeading
pubmed-meshheading:14511320-Animals, pubmed-meshheading:14511320-Blotting, Western, pubmed-meshheading:14511320-Cell Death, pubmed-meshheading:14511320-Cells, Cultured, pubmed-meshheading:14511320-DNA Fragmentation, pubmed-meshheading:14511320-Dose-Response Relationship, Drug, pubmed-meshheading:14511320-Drug Administration Schedule, pubmed-meshheading:14511320-Embryo, Mammalian, pubmed-meshheading:14511320-Ethidium, pubmed-meshheading:14511320-Immunohistochemistry, pubmed-meshheading:14511320-Mice, pubmed-meshheading:14511320-Mice, Knockout, pubmed-meshheading:14511320-Neocortex, pubmed-meshheading:14511320-Neuroglia, pubmed-meshheading:14511320-Neurons, pubmed-meshheading:14511320-Poly(ADP-ribose) Polymerases, pubmed-meshheading:14511320-Poly Adenosine Diphosphate Ribose, pubmed-meshheading:14511320-Reactive Oxygen Species, pubmed-meshheading:14511320-Time Factors, pubmed-meshheading:14511320-Zinc
pubmed:year
2003
pubmed:articleTitle
Involvement of poly ADP ribosyl polymerase-1 in acute but not chronic zinc toxicity.
pubmed:affiliation
Department of Neurology and, Center for the Study of Nervous System Injury, Washington University School of Medicine, 660 S. Euclid Ave, St. Louis, MO 63110, USA. sheline@neuro.wustl.edu
pubmed:publicationType
Journal Article, Comparative Study, Research Support, U.S. Gov't, P.H.S.