Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
1
pubmed:dateCreated
2002-5-15
pubmed:abstractText
An emerging theme in programmed cell death (PCD) of neurons is that the mechanisms involved depend on the cellular context and the death-inducing stimulus. One particular class of neurons for which it is important to identify the mechanisms of PCD are the dopamine neurons of the substantia nigra, the neurons which degenerate in Parkinson's disease. PCD has been shown to occur in these neurons during normal development and to be induced in neurotoxin models of parkinsonism. Conventional histologic stains and TUNEL labeling have not revealed morphologic differences in the apoptosis observed in these neurons in any context. We now show that in two models of induced PCD in postmitotic dopamine neurons, one induced by early striatal target injury and another induced by the neurotoxin 6-hydroxydopamine (6OHDA), there are differences in the cellular localization and type of caspase cleavage products. Using two antibodies to caspase cleavage products (fractin and AB127), we show that in the target lesion model immunostaining is localized to the nucleus, whereas in the 6OHDA model intense cytoplasmic as well as nuclear staining is observed. Another antibody, AB246, to a caspase cleavage product of spectrin, immunostains apoptotic profiles only in the 6OHDA model. These findings suggest that the cellular compartment and therefore the role of the caspases may differ in apoptosis induced in pathologic settings, such as that due to neurotoxins, from that observed in models of natural or induced natural cell death. It will be important to recognize these differences in the consideration of caspase inhibitors in the treatment of degenerative neurologic disease.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
May
pubmed:issn
0014-4886
pubmed:author
pubmed:copyrightInfo
Copyright 2002 Elsevier Science (USA).
pubmed:issnType
Print
pubmed:volume
175
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1-9
pubmed:dateRevised
2007-11-14
pubmed:meshHeading
pubmed-meshheading:12009755-Actins, pubmed-meshheading:12009755-Animals, pubmed-meshheading:12009755-Antibody Specificity, pubmed-meshheading:12009755-Apoptosis, pubmed-meshheading:12009755-Caspases, pubmed-meshheading:12009755-Cell Compartmentation, pubmed-meshheading:12009755-Cell Nucleus, pubmed-meshheading:12009755-Cytoplasm, pubmed-meshheading:12009755-Disease Models, Animal, pubmed-meshheading:12009755-Dopamine, pubmed-meshheading:12009755-Enzyme Inhibitors, pubmed-meshheading:12009755-Humans, pubmed-meshheading:12009755-Immunohistochemistry, pubmed-meshheading:12009755-Neuroblastoma, pubmed-meshheading:12009755-Neurons, pubmed-meshheading:12009755-Oxidopamine, pubmed-meshheading:12009755-Parkinson Disease, Secondary, pubmed-meshheading:12009755-Peptide Fragments, pubmed-meshheading:12009755-Quinolinic Acid, pubmed-meshheading:12009755-Rats, pubmed-meshheading:12009755-Spectrin, pubmed-meshheading:12009755-Substantia Nigra, pubmed-meshheading:12009755-Tumor Cells, Cultured, pubmed-meshheading:12009755-Tyrosine 3-Monooxygenase
pubmed:year
2002
pubmed:articleTitle
Distinct nuclear and cytoplasmic localization of caspase cleavage products in two models of induced apoptotic death in dopamine neurons of the substantia nigra.
pubmed:affiliation
Department of Neurology, The College of Physicians and Surgeons, Columbia University, New York, New York 10032, USA.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S., Research Support, Non-U.S. Gov't