Linked Life Data

10051227

Source:http://linkedlifedata.com/resource/pubmed/id/10051227

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
1
pubmed:dateCreated
1999-4-26
pubmed:abstractText
Some studies have provided evidence that delayed death of hippocampal CA1 neurons in transient global ischemia occurs by classical apoptosis. Recently, translocation of synaptic zinc has been shown to play a key role in ischemic CA1 neuronal death. With these two lines of evidence, we examined in mouse cortical cultures the possibility that zinc neurotoxicity, slowly triggered over a day, may occur by classical apoptosis. Exposure of cortical cultures to 30-35 microM zinc for 24 h resulted in slowly evolving death of neurons only, while exposure to zinc at higher concentrations ( > or = 40 microM) produced near-complete death of both neurons and glia. DNA agarose gel electrophoresis revealed internucleosomal DNA fragmentation, and the terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling method revealed DNA breaks in degenerating neurons after 24 h exposure to 30-35 microM zinc, suggesting that the death may occur by apoptosis. However, electron-microscopic examinations revealed ultrastructural changes clearly indicative of necrosis, such as marked swelling of intracellular organelles and disruption of cell membranes amid relatively intact nuclear membranes. Furthermore, the slowly triggered zinc neurotoxicity was not attenuated by cycloheximide, neurotrophins (brain-derived neurotrophic factor, neurotrophin-3, neurotrophin-4/5) or high potassium, all of which effectively reduced several forms of apoptosis in our cortical cultures. Interestingly, a vitamin E analogue trolox almost completely blocked slowly triggered zinc neurotoxicity, indicating that free radical injury is the main mechanism of zinc neurotoxicity. Consistently, exposure to zinc increased membrane lipid peroxidation assessed by the thiobarbituric acid reactive substance assay. Although zinc-induced neuronal death, slowly triggered over a day, is associated with DNA fragmentation, overall it exhibited features more typical of necrosis. This neuronal death is probably mediated by free radical injury. Further studies appear warranted to investigate the mechanistic link between toxic zinc influx and free radical generation and the possibility that selective neuronal death in transient global ischemia also occurs by zinc-triggered neuronal death exhibiting features of both apoptosis and necrosis.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Mar
pubmed:issn
0306-4522
pubmed:author
pubmed:issnType
Print
pubmed:volume
89
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
175-82
pubmed:dateRevised
2006-11-15
pubmed:meshHeading
pubmed-meshheading:10051227-Animals, pubmed-meshheading:10051227-Antioxidants, pubmed-meshheading:10051227-Apoptosis, pubmed-meshheading:10051227-Brain-Derived Neurotrophic Factor, pubmed-meshheading:10051227-Chromans, pubmed-meshheading:10051227-Cycloheximide, pubmed-meshheading:10051227-DNA Fragmentation, pubmed-meshheading:10051227-Free Radicals, pubmed-meshheading:10051227-In Situ Nick-End Labeling, pubmed-meshheading:10051227-Iron, pubmed-meshheading:10051227-L-Lactate Dehydrogenase, pubmed-meshheading:10051227-Mice, pubmed-meshheading:10051227-Mice, Inbred ICR, pubmed-meshheading:10051227-Microscopy, Electron, pubmed-meshheading:10051227-Necrosis, pubmed-meshheading:10051227-Neurons, pubmed-meshheading:10051227-Potassium, pubmed-meshheading:10051227-Protein Synthesis Inhibitors, pubmed-meshheading:10051227-Zinc
pubmed:year
1999
pubmed:articleTitle
Zinc-induced cortical neuronal death with features of apoptosis and necrosis: mediation by free radicals.
pubmed:affiliation
Department of Neurology, University of Ulsan School of Medicine and Asan Medical Center, Seoul, Korea.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't