Document Detail


Cell death signaling in the cerebellum in Creutzfeldt-Jakob disease.
MedLine Citation:
PMID:  11585244     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Examination of the expression of proteins linked with signaling pathways commanding cell death and cell survival has been carried out to increase understanding on the mechanisms leading to cell death in the cerebellum in Creutzfeldt-Jakob disease (CJD). Expression of Fas, Fas ligand (Fas-L), ERK, MEK, Bcl-2, Bax, N-myc, c-myc, pro-caspase-2 and active caspase-3 was examined by immunohistochemistry in the cerebellum of six patients with sporadic CJD, three patients with olivopontocerebellar atrophy (OPCA) and six age-matched controls. No modifications in the expression of these proteins were observed in granule cells in CJD and OPCA when compared with controls, except in a few cells in the molecular and granular layers in CJD that displayed dense homogeneous active caspase-3 immunostaining. This suggests selective activation of caspase-3 in association with increased cellular vulnerability in CJD. No modifications in pro-caspase-2 and c-myc immunoreactivity were observed in Purkinje cells in diseased brains when compared with controls. However, increased diffuse Fas, Fas-L, MEK, ERK and Bax expression, and enhanced granular active caspase-3 immunoreactivity was found in the cytoplasm of Purkinje cells in CJD. Increase in Bcl-2 and N-myc occurred in Purkinje cells in CJD and OPCA. These results indicate that enhanced Fas, Fas-L, MERK, ERK, Bax and granular active caspase-3 expression is not lethal to Purkinje cells in CJD, whereas increased Bcl-2 and N-myc does not preclude per se cell death or death survival in CJD and OPCA. These findings point to the likelihood that expression of these cell death proteins in neurodegeneration has functional roles differing from those related with apoptosis.
Authors:
B Puig; I Ferrer
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Acta neuropathologica     Volume:  102     ISSN:  0001-6322     ISO Abbreviation:  Acta Neuropathol.     Publication Date:  2001 Sep 
Date Detail:
Created Date:  2001-10-04     Completed Date:  2002-01-24     Revised Date:  2009-11-19    
Medline Journal Info:
Nlm Unique ID:  0412041     Medline TA:  Acta Neuropathol     Country:  Germany    
Other Details:
Languages:  eng     Pagination:  207-15     Citation Subset:  IM    
Affiliation:
Departament de Biologia Cellular i Anatomia Patòlogica, Universitat de Barcelona, Hospitalet de Llobregat, Spain.
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MeSH Terms
Descriptor/Qualifier:
Antigens, CD95 / analysis
Apoptosis / physiology*
Caspase 2
Caspase 3
Caspases / analysis
Cerebellum / pathology*,  physiopathology*
Creutzfeldt-Jakob Syndrome / pathology*,  physiopathology*
Enzyme Precursors / analysis
Fas Ligand Protein
Humans
Immunohistochemistry
Membrane Glycoproteins / analysis
Mitogen-Activated Protein Kinase Kinases / analysis
Mitogen-Activated Protein Kinases / analysis
Olivopontocerebellar Atrophies / pathology,  physiopathology
Proto-Oncogene Proteins / analysis
Proto-Oncogene Proteins c-bcl-2 / analysis
Proto-Oncogene Proteins c-myc / analysis
Signal Transduction / physiology*
bcl-2-Associated X Protein
Chemical
Reg. No./Substance:
0/Antigens, CD95; 0/BAX protein, human; 0/Enzyme Precursors; 0/FASLG protein, human; 0/Fas Ligand Protein; 0/Membrane Glycoproteins; 0/Proto-Oncogene Proteins; 0/Proto-Oncogene Proteins c-bcl-2; 0/Proto-Oncogene Proteins c-myc; 0/bcl-2-Associated X Protein; EC 2.7.11.24/Mitogen-Activated Protein Kinases; EC 2.7.12.2/Mitogen-Activated Protein Kinase Kinases; EC 3.4.22.-/CASP3 protein, human; EC 3.4.22.-/Caspase 2; EC 3.4.22.-/Caspase 3; EC 3.4.22.-/Caspases

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


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