Linked Life Data

9743565

Source:http://linkedlifedata.com/resource/pubmed/id/9743565

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
1
pubmed:dateCreated
1998-10-19
pubmed:abstractText
Increasing evidence indicates that neurons die by apoptosis, an active form of cell death involving a relatively stereotyped series of biochemical changes that culminate in nuclear fragmentation, in many different developmental and pathophysiological settings. In contrast to most other cell types, neurons have elaborate morphologies with complex neuritic arbors that often extend great distances from the cell body. Neuronal death signals are likely to be activated at remote synaptic sites and, indeed, overactivation of glutamate receptors and underactivation of trophic factor receptors are implicated in neurodegenerative disorders. We now report that biochemical changes consistent with apoptosis are engaged locally in synapses. Exposure of cortical synaptosomes to staurosporine and Fe2+ resulted in loss of membrane phospholipid asymmetry, caspase activation, and mitochondrial alterations (membrane depolarization, calcium overload, and oxyradical accumulation) characteristic of apoptosis. The caspase inhibitor zVAD-fmk prevented mitochondrial membrane depolarization in synaptosomes. Studies of the effects of cytosolic extracts from synaptosomes exposed to apoptotic insults, on isolated nuclei, showed that signals capable of inducing nuclear apoptosis are generated locally in synapses. Exposure of cultured hippocampal neurons to staurosporine and glutamate resulted in caspase activation and mitochondrial membrane depolarization in dendrites, and zVAD-fmk prevented the membrane depolarization. Glutamate-induced increases in caspase activity were first observed in dendrites and later in the cell body, and focal application of glutamate to individual dendrites resulted in local activation of caspases. Collectively, the data demonstrate that apoptotic biochemical cascades can be activated locally in synapses and dendrites and suggest a role for such local apoptotic signals in synapse loss and neuronal death in neurodegenerative disorders that involve excessive activation of glutamate receptors.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Sep
pubmed:issn
0014-4886
pubmed:author
pubmed:copyrightInfo
Copyright 1998 Academic Press.
pubmed:issnType
Print
pubmed:volume
153
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
35-48
pubmed:dateRevised
2007-11-14
pubmed:meshHeading
pubmed-meshheading:9743565-Animals, pubmed-meshheading:9743565-Annexin A5, pubmed-meshheading:9743565-Apoptosis, pubmed-meshheading:9743565-Biological Markers, pubmed-meshheading:9743565-Blotting, Western, pubmed-meshheading:9743565-Calcium, pubmed-meshheading:9743565-Caspase 3, pubmed-meshheading:9743565-Caspases, pubmed-meshheading:9743565-Cell Nucleus, pubmed-meshheading:9743565-Cell-Free System, pubmed-meshheading:9743565-Cells, Cultured, pubmed-meshheading:9743565-Cysteine Endopeptidases, pubmed-meshheading:9743565-Cysteine Proteinase Inhibitors, pubmed-meshheading:9743565-Female, pubmed-meshheading:9743565-Glutamic Acid, pubmed-meshheading:9743565-Hippocampus, pubmed-meshheading:9743565-Membrane Potentials, pubmed-meshheading:9743565-Neurons, pubmed-meshheading:9743565-Rats, pubmed-meshheading:9743565-Rats, Sprague-Dawley, pubmed-meshheading:9743565-Reactive Oxygen Species, pubmed-meshheading:9743565-Synapses, pubmed-meshheading:9743565-Synaptosomes
pubmed:year
1998
pubmed:articleTitle
Evidence for synaptic apoptosis.
pubmed:affiliation
Department of Anatomy and Neurobiology, University of Kentucky, Lexington, Kentucky, USA.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S., Research Support, Non-U.S. Gov't