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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 |
2005-10-24
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pubmed:abstractText |
Neural stem/progenitor cells (NPCs) are present in the developing and adult central nervous system. NPC apoptosis is an important aspect of normal brain development. We show that tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) receptor 2 is highly expressed on human NPCs derived from fetal cortex, yet TRAIL induces only minimal levels of apoptosis in NPCs. Caspase-8 mRNA and protein, an important factor in the TRAIL-mediated death pathway, is present at low levels in human NPCs. In contrast, inhibitors of apoptosis proteins (IAP), such as c-IAP1, are highly expressed. The transcription inhibitor actinomycin D sensitized human NPCs to TRAIL-induced apoptosis. Further, inhibition of cellular inhibitors of apoptosis protein 1 (c-IAP1) expression by small interfering RNA (siRNA) increased TRAIL-mediated caspase-3 activation and apoptosis; thus, c-IAP1 protects NPCs against TRAIL-induced apoptosis and suppresses caspase-3 activation. These findings illustrate the mechanisms for NPC resistance to apoptotic agonists such as TRAIL, and demonstrate a potentially important mechanism in CNS disease states.
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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/Apoptosis Regulatory Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/BIRC2 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/CASP3 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/CASP8 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Caspase 3,
http://linkedlifedata.com/resource/pubmed/chemical/Caspase 8,
http://linkedlifedata.com/resource/pubmed/chemical/Caspases,
http://linkedlifedata.com/resource/pubmed/chemical/Dactinomycin,
http://linkedlifedata.com/resource/pubmed/chemical/Inhibitor of Apoptosis Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Membrane Glycoproteins,
http://linkedlifedata.com/resource/pubmed/chemical/Protein Synthesis Inhibitors,
http://linkedlifedata.com/resource/pubmed/chemical/RNA, Messenger,
http://linkedlifedata.com/resource/pubmed/chemical/Receptors, TNF-Related...,
http://linkedlifedata.com/resource/pubmed/chemical/Receptors, Tumor Necrosis Factor,
http://linkedlifedata.com/resource/pubmed/chemical/TNF-Related Apoptosis-Inducing...,
http://linkedlifedata.com/resource/pubmed/chemical/TNFRSF10B protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/TNFSF10 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Tumor Necrosis Factor-alpha
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pubmed:status |
MEDLINE
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pubmed:month |
Nov
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pubmed:issn |
0360-4012
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pubmed:author |
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pubmed:copyrightInfo |
Copyright (c) 2005 Wiley-Liss, Inc.
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pubmed:issnType |
Print
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pubmed:day |
1
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pubmed:volume |
82
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
295-305
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pubmed:dateRevised |
2007-11-14
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pubmed:meshHeading |
pubmed-meshheading:16180223-Apoptosis,
pubmed-meshheading:16180223-Apoptosis Regulatory Proteins,
pubmed-meshheading:16180223-Brain,
pubmed-meshheading:16180223-Caspase 3,
pubmed-meshheading:16180223-Caspase 8,
pubmed-meshheading:16180223-Caspases,
pubmed-meshheading:16180223-Cells, Cultured,
pubmed-meshheading:16180223-Cerebral Cortex,
pubmed-meshheading:16180223-Dactinomycin,
pubmed-meshheading:16180223-Enzyme Activation,
pubmed-meshheading:16180223-Fetus,
pubmed-meshheading:16180223-Humans,
pubmed-meshheading:16180223-Inhibitor of Apoptosis Proteins,
pubmed-meshheading:16180223-Membrane Glycoproteins,
pubmed-meshheading:16180223-Nerve Degeneration,
pubmed-meshheading:16180223-Neurons,
pubmed-meshheading:16180223-Protein Synthesis Inhibitors,
pubmed-meshheading:16180223-RNA, Messenger,
pubmed-meshheading:16180223-RNA Interference,
pubmed-meshheading:16180223-Receptors, TNF-Related Apoptosis-Inducing Ligand,
pubmed-meshheading:16180223-Receptors, Tumor Necrosis Factor,
pubmed-meshheading:16180223-Stem Cells,
pubmed-meshheading:16180223-TNF-Related Apoptosis-Inducing Ligand,
pubmed-meshheading:16180223-Tumor Necrosis Factor-alpha,
pubmed-meshheading:16180223-Up-Regulation
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pubmed:year |
2005
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pubmed:articleTitle |
Cellular IAP1 regulates TRAIL-induced apoptosis in human fetal cortical neural progenitor cells.
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pubmed:affiliation |
Laboratory of Neurotoxicology at the Center for Neurovirology and Neurodegenerative Disorders, University of Nebraska Medical Center, Omaha, Nebraska.
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pubmed:publicationType |
Journal Article,
Research Support, N.I.H., Extramural
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