Document Detail


Role of heat shock response and Hsp27 in mutant SOD1-dependent cell death.
MedLine Citation:
PMID:  16806187     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
The fatal neurodegenerative disorder amyotrophic lateral sclerosis (ALS) is characterized by selective loss of motor neurons and mutations in the copper-zinc superoxide dismutase (SOD1) enzyme underlie one form of familial ALS. The pathogenic mechanism of these mutations is elusive but is thought to involve oxidative stress and protein aggregation. These two phenomena are known to induce heat shock proteins (Hsps) which protect stressed cells through their chaperoning and anti-apoptotic activity. In order to investigate the role of Hsp27 in mutant SOD1-dependent cell death, we used mutant and wild type SOD1 overexpressing N2a mouse neuroblastoma cells. Mutant SOD1-dependent cell death could be induced by heat shock, and by treating the cells with cyclosporine A or lactacystin. Transfection with an Hsp27 expression construct did not protect the N2a cells against mutant SOD1-dependent cell death. However, pre-conditioning N2a cells with a mild heat shock was accompanied by a significant upregulation of Hsp27 in the mutant SOD1 cells, and protected these cells against subsequent cell death induced by a more severe heat shock. Selective inhibition of the Hsp27 upregulation, through the use of Hsp27 siRNA, did not attenuate the protective effect of this treatment. These results show that activation of the heat shock response protects cells against mutant SOD1-dependent cell death, but that Hsp27 is not an essential component of the stress response leading to protection.
Authors:
J Krishnan; R Lemmens; W Robberecht; L Van Den Bosch
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Publication Detail:
Type:  Comparative Study; Journal Article; Research Support, Non-U.S. Gov't     Date:  2006-06-27
Journal Detail:
Title:  Experimental neurology     Volume:  200     ISSN:  0014-4886     ISO Abbreviation:  Exp. Neurol.     Publication Date:  2006 Aug 
Date Detail:
Created Date:  2006-07-31     Completed Date:  2006-09-21     Revised Date:  2008-11-21    
Medline Journal Info:
Nlm Unique ID:  0370712     Medline TA:  Exp Neurol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  301-10     Citation Subset:  IM    
Affiliation:
Laboratory of Neurobiology, K.U.Leuven, Campus Gasthuisberg, Leuven, Belgium.
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MeSH Terms
Descriptor/Qualifier:
Animals
Antirheumatic Agents / pharmacology
Blotting, Western / methods
Cell Death / drug effects,  genetics
Cell Line, Tumor
Cyclosporine / pharmacology
HSP27 Heat-Shock Proteins
Heat-Shock Proteins / physiology*
Heat-Shock Response / drug effects,  physiology*
Humans
Immunohistochemistry / methods
Mice
Mutagenesis / physiology
Mutant Proteins / genetics*
Neuroblastoma
RNA, Messenger / metabolism
RNA, Small Interfering / pharmacology
Reverse Transcriptase Polymerase Chain Reaction / methods
Superoxide Dismutase / genetics*
Time Factors
Transfection / methods
Chemical
Reg. No./Substance:
0/Antirheumatic Agents; 0/HSP27 Heat-Shock Proteins; 0/Heat-Shock Proteins; 0/Hspb2 protein, mouse; 0/Mutant Proteins; 0/RNA, Messenger; 0/RNA, Small Interfering; 59865-13-3/Cyclosporine; EC 1.15.1.-/superoxide dismutase 1; EC 1.15.1.1/Superoxide Dismutase

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


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