Source:http://linkedlifedata.com/resource/pubmed/id/10516294
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| Predicate | Object |
|---|---|
| rdf:type | |
| lifeskim:mentions | |
| pubmed:issue |
20
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| pubmed:dateCreated |
1999-10-28
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| pubmed:abstractText |
Cerebellar granule neurons (CGNs) undergo apoptosis when deprived of depolarizing concentrations of KCl, but the underlying molecular mechanisms are not yet clear. Although caspases have been postulated to be involved in CGN cell death, inhibitors of caspases failed to prevent apoptosis under our culture conditions, suggesting an involvement of other molecules and pathways. We find that inhibitors of cyclin-dependent kinases--flavopiridol, olomoucine, and roscovitine--protect CGNs from KCl withdrawal-induced apoptosis, suggesting that cell cycle components play a significant role in the death of these neurons. Analysis of the different cell cycle regulatory elements in this model revealed that apoptosis is preceded by an increase in the level of cyclin E protein, with elevated nuclear levels of cyclin D1 and with enhanced activity of the cyclin D1- and E- associated kinases. In addition, there was a significant decrease in the level of the cyclin-dependent kinase (cdk) inhibitor p27. In agreement with these changes, analysis of a major substrate of cyclin-activated cdks, retinoblastoma protein (Rb), showed an increase in the level of phosphorylated forms within 1 hr of KCl withdrawal. Moreover, the overall levels of Rb protein were significantly reduced within 6-12 hr of KCl withdrawal and did so by a caspase-independent mechanism. All of these responses were blocked by cdk inhibitors. These findings indicate that cdks act at an early step in the pathway by which KCl withdrawal induces apoptotic death of cerebellar granule cells and suggest that additional elements of the cell cycle machinery participate in this mechanism.
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| pubmed:grant | |
| pubmed:language |
eng
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| pubmed:journal | |
| pubmed:citationSubset |
IM
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| pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Ccng1 protein, rat,
http://linkedlifedata.com/resource/pubmed/chemical/Cdkn1b protein, rat,
http://linkedlifedata.com/resource/pubmed/chemical/Cell Cycle Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Cyclin G,
http://linkedlifedata.com/resource/pubmed/chemical/Cyclin G1,
http://linkedlifedata.com/resource/pubmed/chemical/Cyclin-Dependent Kinase Inhibitor...,
http://linkedlifedata.com/resource/pubmed/chemical/Cyclin-Dependent Kinases,
http://linkedlifedata.com/resource/pubmed/chemical/Cyclins,
http://linkedlifedata.com/resource/pubmed/chemical/Enzyme Inhibitors,
http://linkedlifedata.com/resource/pubmed/chemical/Microtubule-Associated Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Potassium Chloride,
http://linkedlifedata.com/resource/pubmed/chemical/Retinoblastoma Protein,
http://linkedlifedata.com/resource/pubmed/chemical/Tumor Suppressor Proteins
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| pubmed:status |
MEDLINE
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| pubmed:month |
Oct
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| pubmed:issn |
1529-2401
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| pubmed:author | |
| pubmed:issnType |
Electronic
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| pubmed:day |
15
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| pubmed:volume |
19
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| pubmed:owner |
NLM
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| pubmed:authorsComplete |
Y
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| pubmed:pagination |
8747-56
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| pubmed:dateRevised |
2009-11-19
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| pubmed:meshHeading |
pubmed-meshheading:10516294-Animals,
pubmed-meshheading:10516294-Apoptosis,
pubmed-meshheading:10516294-Cell Cycle Proteins,
pubmed-meshheading:10516294-Cells, Cultured,
pubmed-meshheading:10516294-Cerebellum,
pubmed-meshheading:10516294-Cyclin G,
pubmed-meshheading:10516294-Cyclin G1,
pubmed-meshheading:10516294-Cyclin-Dependent Kinase Inhibitor p27,
pubmed-meshheading:10516294-Cyclin-Dependent Kinases,
pubmed-meshheading:10516294-Cyclins,
pubmed-meshheading:10516294-Enzyme Inhibitors,
pubmed-meshheading:10516294-Microtubule-Associated Proteins,
pubmed-meshheading:10516294-Neurons,
pubmed-meshheading:10516294-Phosphorylation,
pubmed-meshheading:10516294-Potassium Chloride,
pubmed-meshheading:10516294-Rats,
pubmed-meshheading:10516294-Rats, Sprague-Dawley,
pubmed-meshheading:10516294-Retinoblastoma Protein,
pubmed-meshheading:10516294-Tumor Suppressor Proteins
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| pubmed:year |
1999
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| pubmed:articleTitle |
Role of cell cycle regulatory proteins in cerebellar granule neuron apoptosis.
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| pubmed:affiliation |
Department of Pathology and Center for Neurobiology and Behavior, Taub Center for Alzheimer's Disease Research, College of Physicians and Surgeons, Columbia University, New York, New York 10032, USA.
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| pubmed:publicationType |
Journal Article,
Research Support, U.S. Gov't, P.H.S.,
Research Support, Non-U.S. Gov't
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