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Predicate | Object |
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rdf:type | |
lifeskim:mentions | |
pubmed:issue |
2
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pubmed:dateCreated |
1999-1-7
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pubmed:abstractText |
Activation of proteolytic enzymes, including the caspase family of proteinases, is a feature characteristic of the apoptotic program. In the present study, we examined a potential role of intracellular proteinases in the death of neuronal PC12 and primary cultured rat microglial cells induced by 6-hydroxydopamine (6-OHDA). In both neuronal PC12 and microglial cells, 6-OHDA (10-200 microM) induced apoptosis in a dose-dependent manner as judged by the DNA break. The 6-OHDA was ineffective in Bcl-2-overexpressing neuronal PC12 cells. Pretreatment of these cells with two caspase inhibitors, acetyl-Try-Val-Ala-Asp-aldehyde and acetyl-Asp-Glu-Val-Asp-aldehyde, prevented the 6-OHDA-induced apoptosis. Pepstatin A and leupeptin, potent inhibitors of aspartic and cysteine proteinases, respectively, partly inhibited the apoptosis of microglia but not neuronal PC12 cells. In contrast, GBR12935, a dopamine uptake inhibitor, significantly inhibited the apoptotic death of neuronal PC12 cells but not microglia. These results suggest that mechanisms by which 6-OHDA induces apoptosis in these two cell types are distinct; 6-OHDA incorporated into neuronal PC12 cells and its metabolites may activate the caspase-like enzymes, whereas oxidative metabolites of the agent produced extracellularly may activate the caspase and the endosomal/lysosomal proteolytic systems in microglia.
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pubmed:language |
eng
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pubmed:journal | |
pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Caspases,
http://linkedlifedata.com/resource/pubmed/chemical/GBR 12935,
http://linkedlifedata.com/resource/pubmed/chemical/Ligands,
http://linkedlifedata.com/resource/pubmed/chemical/Oxidopamine,
http://linkedlifedata.com/resource/pubmed/chemical/Piperazines,
http://linkedlifedata.com/resource/pubmed/chemical/Protease Inhibitors
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pubmed:status |
MEDLINE
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pubmed:month |
Oct
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pubmed:issn |
0360-4012
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pubmed:author | |
pubmed:issnType |
Print
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pubmed:day |
15
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pubmed:volume |
54
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
214-22
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pubmed:dateRevised |
2006-11-15
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pubmed:meshHeading |
pubmed-meshheading:9788280-Animals,
pubmed-meshheading:9788280-Apoptosis,
pubmed-meshheading:9788280-Caspases,
pubmed-meshheading:9788280-Cell Survival,
pubmed-meshheading:9788280-Cells, Cultured,
pubmed-meshheading:9788280-Enzyme Induction,
pubmed-meshheading:9788280-Genes, bcl-2,
pubmed-meshheading:9788280-In Situ Nick-End Labeling,
pubmed-meshheading:9788280-Ligands,
pubmed-meshheading:9788280-Microglia,
pubmed-meshheading:9788280-Oxidopamine,
pubmed-meshheading:9788280-PC12 Cells,
pubmed-meshheading:9788280-Piperazines,
pubmed-meshheading:9788280-Protease Inhibitors,
pubmed-meshheading:9788280-Rats
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pubmed:year |
1998
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pubmed:articleTitle |
Involvement of caspase-like proteinases in apoptosis of neuronal PC12 cells and primary cultured microglia induced by 6-hydroxydopamine.
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pubmed:affiliation |
Department of Pharmacology, Faculty of Dentistry, Kyushu University, Fukuoka, Japan.
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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