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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
7
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pubmed:dateCreated |
2005-6-16
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pubmed:abstractText |
Prion protein (PrP) prevents Bcl-2-associated protein X (Bax)-mediated cell death, but the step at which PrP inhibits is not known. We first show that PrP is very specific for Bax and cannot prevent Bak (Bcl-2 antagonist killer 1)-, tBid-, staurosporine- or thapsigargin-mediated cell death. As Bax activation involves Bax conformational change, mitochondrial translocation, cytochrome c release and caspase activation, we investigated which of these events was inhibited by PrP. PrP inhibits Bax conformational change, cytochrome c release and cell death in human primary neurons and MCF-7 cells. Serum deprivation-induced Bax conformational change is more rapid in PrP-null cells. PrP does not prevent active caspase-mediated cell death. PrP does not colocalize with Bax in normal or apoptotic primary neurons and cannot prevent Bax-mediated cytochrome c release in a mitochondrial cell-free system. We conclude that PrP protects against Bax-mediated cell death by preventing the Bax proapoptotic conformational change that occurs initially in Bax activation.
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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/BAK1 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/BAX protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/BH3 Interacting Domain Death...,
http://linkedlifedata.com/resource/pubmed/chemical/BID protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/CASP6 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Carrier Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Caspase 6,
http://linkedlifedata.com/resource/pubmed/chemical/Cysteine Endopeptidases,
http://linkedlifedata.com/resource/pubmed/chemical/Cytochromes c,
http://linkedlifedata.com/resource/pubmed/chemical/Enzyme Inhibitors,
http://linkedlifedata.com/resource/pubmed/chemical/Membrane Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/PrPC Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Proto-Oncogene Proteins c-bcl-2,
http://linkedlifedata.com/resource/pubmed/chemical/Thapsigargin,
http://linkedlifedata.com/resource/pubmed/chemical/bcl-2 Homologous Antagonist-Killer...,
http://linkedlifedata.com/resource/pubmed/chemical/bcl-2-Associated X Protein
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pubmed:status |
MEDLINE
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pubmed:month |
Jul
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pubmed:issn |
1350-9047
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pubmed:author |
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pubmed:issnType |
Print
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pubmed:volume |
12
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
783-95
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pubmed:dateRevised |
2007-11-14
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pubmed:meshHeading |
pubmed-meshheading:15846375-Apoptosis,
pubmed-meshheading:15846375-BH3 Interacting Domain Death Agonist Protein,
pubmed-meshheading:15846375-Breast Neoplasms,
pubmed-meshheading:15846375-Carrier Proteins,
pubmed-meshheading:15846375-Caspase 6,
pubmed-meshheading:15846375-Cell Line, Tumor,
pubmed-meshheading:15846375-Cysteine Endopeptidases,
pubmed-meshheading:15846375-Cytochromes c,
pubmed-meshheading:15846375-Enzyme Inhibitors,
pubmed-meshheading:15846375-Female,
pubmed-meshheading:15846375-Humans,
pubmed-meshheading:15846375-Membrane Proteins,
pubmed-meshheading:15846375-Mitochondria,
pubmed-meshheading:15846375-Neurons,
pubmed-meshheading:15846375-PrPC Proteins,
pubmed-meshheading:15846375-Protein Structure, Quaternary,
pubmed-meshheading:15846375-Protein Transport,
pubmed-meshheading:15846375-Proto-Oncogene Proteins c-bcl-2,
pubmed-meshheading:15846375-Thapsigargin,
pubmed-meshheading:15846375-bcl-2 Homologous Antagonist-Killer Protein,
pubmed-meshheading:15846375-bcl-2-Associated X Protein
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pubmed:year |
2005
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pubmed:articleTitle |
Cellular prion protein inhibits proapoptotic Bax conformational change in human neurons and in breast carcinoma MCF-7 cells.
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pubmed:affiliation |
The Bloomfield Center for Research in Aging, Lady Davis Institute for Medical Research, The Sir Mortimer B Davis Jewish General Hospital, Montréal, Québec, Canada.
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pubmed:publicationType |
Journal Article,
Research Support, U.S. Gov't, P.H.S.,
Research Support, Non-U.S. Gov't,
Research Support, N.I.H., Extramural
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