Document Detail


Caspase-8 is required for cell death induced by expanded polyglutamine repeats.
MedLine Citation:
PMID:  10197541     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
We show here that caspase-8 is required for the death of primary rat neurons induced by an expanded polyglutamine repeat (Q79). Expression of Q79 recruited and activated caspase-8. Inhibition of caspase-8 blocked polyglutamine-induced cell death. Coexpression of Q79 with the caspase inhibitor CrmA, a dominant-negative mutant of FADD (FADD DN), Bcl-2, or Bcl-xL, but not an N-terminally tagged Bcl-xL, prevented the recruitment of caspase-8 and inhibited polyglutamine-induced cell death. Furthermore, Western blot analysis revealed the presence of activated caspase-8 in the insoluble fraction of affected brain regions from Huntington's disease (HD) patients but not in those from neurologically unremarkable controls, suggesting the relocation and activation of caspase-8 during the pathogenesis of HD. These results suggest an essential role of caspase-8 in HD-related neural degenerative diseases.
Authors:
I Sánchez; C J Xu; P Juo; A Kakizaka; J Blenis; J Yuan
Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  Neuron     Volume:  22     ISSN:  0896-6273     ISO Abbreviation:  Neuron     Publication Date:  1999 Mar 
Date Detail:
Created Date:  1999-04-27     Completed Date:  1999-04-27     Revised Date:  2007-11-14    
Medline Journal Info:
Nlm Unique ID:  8809320     Medline TA:  Neuron     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  623-33     Citation Subset:  IM    
Affiliation:
Department of Cell Biology, Harvard Medical School, Boston, Massachusetts 02115, USA.
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MeSH Terms
Descriptor/Qualifier:
Adaptor Proteins, Signal Transducing*
Animals
Apoptosis / physiology*
Carrier Proteins / biosynthesis,  metabolism
Caspase 8
Caspase 9
Caspases / antagonists & inhibitors,  genetics,  physiology*
Cell Line
Cysteine Proteinase Inhibitors / biosynthesis,  metabolism
Enzyme Activation
Fas-Associated Death Domain Protein
Fluorescent Antibody Technique, Direct
Humans
Immunoblotting
Microscopy, Confocal
Mutation
Neurons / enzymology,  physiology*
Peptides / physiology*
Plasmids
Proto-Oncogene Proteins c-bcl-2 / biosynthesis,  metabolism
Rats
Repetitive Sequences, Amino Acid
Serpins / biosynthesis,  metabolism
Viral Proteins*
Grant Support
ID/Acronym/Agency:
NS31862/NS/NINDS NIH HHS
Chemical
Reg. No./Substance:
0/Adaptor Proteins, Signal Transducing; 0/Carrier Proteins; 0/Cysteine Proteinase Inhibitors; 0/FADD protein, human; 0/Fadd protein, rat; 0/Fas-Associated Death Domain Protein; 0/Peptides; 0/Proto-Oncogene Proteins c-bcl-2; 0/Serpins; 0/Viral Proteins; 26700-71-0/polyglutamine; 96282-35-8/interleukin-1beta-converting enzyme inhibitor; EC 3.4.22.-/CASP8 protein, human; EC 3.4.22.-/CASP9 protein, human; EC 3.4.22.-/Casp8 protein, rat; EC 3.4.22.-/Casp9 protein, rat; EC 3.4.22.-/Caspase 8; EC 3.4.22.-/Caspase 9; EC 3.4.22.-/Caspases
Comments/Corrections
Comment In:
Neuron. 1999 Mar;22(3):416-7   [PMID:  10197520 ]

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