Document Detail


Cellular prion protein inhibits proapoptotic Bax conformational change in human neurons and in breast carcinoma MCF-7 cells.
MedLine Citation:
PMID:  15846375     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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.
Authors:
X Roucou; P N Giannopoulos; Y Zhang; J Jodoin; C G Goodyer; A LeBlanc
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  Cell death and differentiation     Volume:  12     ISSN:  1350-9047     ISO Abbreviation:  Cell Death Differ.     Publication Date:  2005 Jul 
Date Detail:
Created Date:  2005-06-16     Completed Date:  2005-09-29     Revised Date:  2007-11-14    
Medline Journal Info:
Nlm Unique ID:  9437445     Medline TA:  Cell Death Differ     Country:  England    
Other Details:
Languages:  eng     Pagination:  783-95     Citation Subset:  IM    
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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MeSH Terms
Descriptor/Qualifier:
Apoptosis* / drug effects
BH3 Interacting Domain Death Agonist Protein
Breast Neoplasms / metabolism*,  pathology
Carrier Proteins / metabolism
Caspase 6
Cell Line, Tumor
Cysteine Endopeptidases / metabolism
Cytochromes c / metabolism
Enzyme Inhibitors / pharmacology
Female
Humans
Membrane Proteins / metabolism
Mitochondria / metabolism
Neurons / drug effects,  metabolism*
PrPC Proteins / metabolism*
Protein Structure, Quaternary
Protein Transport / drug effects
Proto-Oncogene Proteins c-bcl-2 / antagonists & inhibitors,  chemistry*,  metabolism*
Thapsigargin / pharmacology
bcl-2 Homologous Antagonist-Killer Protein
bcl-2-Associated X Protein
Grant Support
ID/Acronym/Agency:
R01 NS40431/NS/NINDS NIH HHS
Chemical
Reg. No./Substance:
0/BAK1 protein, human; 0/BAX protein, human; 0/BH3 Interacting Domain Death Agonist Protein; 0/BID protein, human; 0/Carrier Proteins; 0/Enzyme Inhibitors; 0/Membrane Proteins; 0/PrPC Proteins; 0/Proto-Oncogene Proteins c-bcl-2; 0/bcl-2 Homologous Antagonist-Killer Protein; 0/bcl-2-Associated X Protein; 67526-95-8/Thapsigargin; 9007-43-6/Cytochromes c; EC 3.4.22.-/CASP6 protein, human; EC 3.4.22.-/Caspase 6; EC 3.4.22.-/Cysteine Endopeptidases

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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