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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
3
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pubmed:dateCreated |
2005-1-20
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pubmed:abstractText |
We used human neural stem cells (hNSCs) and their differentiated cultures as a model system to evaluate the mechanism(s) involved in rotenone (RO)- and camptothecin (CA)-induced cytotoxicity. Results from ultrastructural damage and terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) staining indicated that RO-induced cytotoxicity resembled CA-induced apoptosis more than H(2)O(2)-induced necrosis. However, unlike CA-induced, caspase 9/3-dependent apoptosis, there was no increased activity in caspase 9, caspase 3 or poly (ADP-ribose) polymerase (PARP) cleavage in RO-induced cytotoxicity, in spite of time-dependent release of cytochrome c and apoptosis-inducing factor (AIF) following mitochondrial membrane depolarization and a significant increase in reactive oxygen species generation. Equal doses of RO and CA used in hNSCs induced caspase 9/3-dependent apoptosis in differentiated cultures. Time-dependent ATP depletion occurred earlier and to a greater extent in RO-treated hNSCs than in CA-treated hNSCs, or differentiated cultures treated with RO or CA. In conclusion, these results represent a unique ultrastructural and molecular characterization of RO- and CA-induced cytotoxicity in hNSCs and their differentiated cultures. Intracellular ATP levels may play an important role in determining whether neural progenitors or their differentiated cells follow a caspase 9/3-dependent or -independent pathway in response to acute insults from neuronal toxicants.
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pubmed:grant |
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Adenosine Triphosphate,
http://linkedlifedata.com/resource/pubmed/chemical/CASP3 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/CASP9 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Camptothecin,
http://linkedlifedata.com/resource/pubmed/chemical/Caspase 3,
http://linkedlifedata.com/resource/pubmed/chemical/Caspase 9,
http://linkedlifedata.com/resource/pubmed/chemical/Caspases,
http://linkedlifedata.com/resource/pubmed/chemical/Enzyme Inhibitors,
http://linkedlifedata.com/resource/pubmed/chemical/Reactive Oxygen Species,
http://linkedlifedata.com/resource/pubmed/chemical/Rotenone,
http://linkedlifedata.com/resource/pubmed/chemical/Topoisomerase I Inhibitors,
http://linkedlifedata.com/resource/pubmed/chemical/Uncoupling Agents
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pubmed:status |
MEDLINE
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pubmed:month |
Feb
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pubmed:issn |
0022-3042
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pubmed:author |
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pubmed:issnType |
Print
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pubmed:volume |
92
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
462-76
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pubmed:dateRevised |
2010-11-18
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pubmed:meshHeading |
pubmed-meshheading:15659217-Adenosine Triphosphate,
pubmed-meshheading:15659217-Camptothecin,
pubmed-meshheading:15659217-Caspase 3,
pubmed-meshheading:15659217-Caspase 9,
pubmed-meshheading:15659217-Caspases,
pubmed-meshheading:15659217-Cell Death,
pubmed-meshheading:15659217-Cell Differentiation,
pubmed-meshheading:15659217-Cells, Cultured,
pubmed-meshheading:15659217-DNA Fragmentation,
pubmed-meshheading:15659217-Dose-Response Relationship, Drug,
pubmed-meshheading:15659217-Enzyme Activation,
pubmed-meshheading:15659217-Enzyme Inhibitors,
pubmed-meshheading:15659217-Humans,
pubmed-meshheading:15659217-In Situ Nick-End Labeling,
pubmed-meshheading:15659217-Models, Biological,
pubmed-meshheading:15659217-Neurons,
pubmed-meshheading:15659217-Reactive Oxygen Species,
pubmed-meshheading:15659217-Rotenone,
pubmed-meshheading:15659217-Stem Cells,
pubmed-meshheading:15659217-Topoisomerase I Inhibitors,
pubmed-meshheading:15659217-Uncoupling Agents
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pubmed:year |
2005
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pubmed:articleTitle |
Rotenone-induced caspase 9/3-independent and -dependent cell death in undifferentiated and differentiated human neural stem cells.
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pubmed:affiliation |
School of Pharmacy, University of Wisconsin at Madison, 777 Highland Avenue, Madison, WI 53705-2222, USA.
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pubmed:publicationType |
Journal Article,
Research Support, U.S. Gov't, P.H.S.,
Research Support, N.I.H., Extramural
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