Document Detail


Cell culture models to investigate the selective vulnerability of motoneuronal mitochondria to familial ALS-linked G93ASOD1.
MedLine Citation:
PMID:  16903849     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Mitochondrial damage induced by superoxide dismutase (SOD1) mutants has been proposed to have a causative role in the selective degeneration of motoneurons in amyotrophic lateral sclerosis (ALS). In order to investigate the basis of the tissue specificity of mutant SOD1 we compared the effect of the continuous expression of wild-type or mutant (G93A) human SOD1 on mitochondrial morphology in the NSC-34 motoneuronal-like, the N18TG2 neuroblastoma and the non-neuronal Madin-Darby Canine Kidney (MDCK) cell lines. Morphological alterations of mitochondria were observed in NSC-34 expressing the G93A mutant (NSC-G93A) but not the wild-type SOD1, whereas a ten-fold greater level of total expression of the mutant had no effect on mitochondria of non-motoneuronal cell lines. Fragmented network, swelling and cristae remodelling but not vacuolization of mitochondria or other intracellular organelles were observed only in NSC-G93A cells. The mitochondrial alterations were not explained by a preferential localization of the mutant within NSC-G93A mitochondria, as a higher amount of the mutant SOD1 was found in mitochondria of MDCK-G93A cells. Our results suggest that mitochondrial vulnerability of motoneurons to G93ASOD1 is recapitulated in NSC-34 cells, and that peculiar features in network dynamics may account for the selective alterations of motoneuronal mitochondria.
Authors:
Andrea Raimondi; Alessandra Mangolini; Milena Rizzardini; Silvia Tartari; Silvia Massari; Caterina Bendotti; Maura Francolini; Nica Borgese; Lavinia Cantoni; Grazia Pietrini
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  The European journal of neuroscience     Volume:  24     ISSN:  0953-816X     ISO Abbreviation:  Eur. J. Neurosci.     Publication Date:  2006 Jul 
Date Detail:
Created Date:  2006-08-14     Completed Date:  2006-10-03     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  8918110     Medline TA:  Eur J Neurosci     Country:  France    
Other Details:
Languages:  eng     Pagination:  387-99     Citation Subset:  IM    
Affiliation:
Department of Pharmacology, School of Medicine, Center of Excellence on Neurodegenerative Diseases, University of Milano, Consiglio Nazionale delle Ricerche, CNR, Institute of Neuroscience, Milano, Italy.
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MeSH Terms
Descriptor/Qualifier:
Amyotrophic Lateral Sclerosis / enzymology*,  genetics*,  physiopathology
Animals
Cell Line, Tumor
Cell Respiration / genetics
Dogs
Gene Expression Regulation, Enzymologic / genetics
Genetic Predisposition to Disease / genetics*
Humans
Mice
Microscopy, Electron, Transmission
Mitochondria / enzymology*,  genetics,  pathology
Mitochondrial Membranes / enzymology,  pathology
Motor Neurons / enzymology*,  pathology
Mutation / genetics
Superoxide Dismutase / genetics*
Chemical
Reg. No./Substance:
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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