Document Detail

Mutant superoxide dismutase-1-linked familial amyotrophic lateral sclerosis: molecular mechanisms of neuronal death and protection.
MedLine Citation:
PMID:  9348345     Owner:  NLM     Status:  MEDLINE    
Mutations in human Cu/Zn superoxide dismutase-1 (SOD) cause approximately 20% of cases of familial amyotrophic lateral sclerosis (FALS). We investigated the mechanism of mutant SOD-induced neuronal degeneration by expressing wild-type and mutant SODs in neuronal cells by means of infection with replication-deficient recombinant adenoviruses. Expression of two FALS-related mutant SODs (A4V and V148G) caused death of differentiated PC12 cells, superior cervical ganglion neurons, and hippocampal pyramidal neurons. Cell death included many features typical of apoptosis. Death could be prevented by copper (Cu2+) chelators, Bcl-2, glutathione, vitamin E, and inhibitors of caspases. Mutant SOD-expressing PC12 cells had higher rates of superoxide (O2-) production under a variety of conditions. The results support the hypothesis that mutant SOD induced-neurodegeneration is associated with disturbances of neuronal free radical homeostasis.
G D Ghadge; J P Lee; V P Bindokas; J Jordan; L Ma; R J Miller; R P Roos
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  The Journal of neuroscience : the official journal of the Society for Neuroscience     Volume:  17     ISSN:  0270-6474     ISO Abbreviation:  J. Neurosci.     Publication Date:  1997 Nov 
Date Detail:
Created Date:  1997-12-08     Completed Date:  1997-12-08     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  8102140     Medline TA:  J Neurosci     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  8756-66     Citation Subset:  IM    
Department of Neurology, The University of Chicago, Chicago, Illinois 60637, USA.
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MeSH Terms
Adenoviridae / genetics
Amyotrophic Lateral Sclerosis / enzymology*,  genetics*
Antioxidants / pharmacology
Apoptosis / genetics
Cell Survival / physiology
Chelating Agents / pharmacology
Family Health
Free Radicals / metabolism
Gene Expression Regulation, Enzymologic
Gene Expression Regulation, Viral
Kidney / cytology
Neurons / cytology*,  drug effects,  enzymology
Oxidative Stress / physiology
PC12 Cells
Recombinant Proteins / metabolism
Superoxide Dismutase / genetics*
Superoxides / metabolism
Reg. No./Substance:
0/Antioxidants; 0/Chelating Agents; 0/Free Radicals; 0/Recombinant Proteins; 11062-77-4/Superoxides; EC Dismutase

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