Document Detail


Inhibition of neurite outgrowth and promotion of cell death by cytoplasmic soluble mutant huntingtin stably transfected in mouse neuroblastoma cells.
MedLine Citation:
PMID:  18650014     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Huntington's disease (HD) is an autosomal dominant inheritable neurodegenerative disorder caused by expansion of a polyglutamine repeat in the amino-terminal region of huntingtin. Polyglutamine expansion causes mutant huntingtin to aggregate and accumulate in the nuclei and cytoplasm of neurons. The aggregated amino-terminal fragments of mutant huntingtin are toxic to neuronal cells and may be involved in the neurodegeneration in HD patient brains. Although nuclear mutant huntingtin has been found to affect gene expression, the effect of cytoplasmic mutant huntingtin remains to be investigated. We established stably transfected mouse neuroblastoma (N2a) cells that express soluble amino-terminal fragments of huntingtin containing 20 (20Q) or 150 (150Q) glutamine repeats. In these stable cell lines, both 20Q and 150Q are diffusely distributed in the cytoplasm without aggregate formation. However, the stable 150Q cells are deficient in neurite outgrowth. Compared with wild-type N2a cells and cells stably expressing 20Q, stable 150Q cells also have decreased viability and are more susceptible to apoptotic stimulation. These findings suggest that the cytoplasmic soluble mutant huntingtin is also toxic to cells.
Authors:
Cuifang Ye; Yinong Zhang; Weixi Wang; Jianzhi Wang; He Li
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2008-06-13
Journal Detail:
Title:  Neuroscience letters     Volume:  442     ISSN:  0304-3940     ISO Abbreviation:  Neurosci. Lett.     Publication Date:  2008 Sep 
Date Detail:
Created Date:  2008-07-29     Completed Date:  2008-10-14     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  7600130     Medline TA:  Neurosci Lett     Country:  Ireland    
Other Details:
Languages:  eng     Pagination:  63-8     Citation Subset:  IM    
Affiliation:
Division of Histology and Embryology, Department of Anatomy, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, PR China.
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MeSH Terms
Descriptor/Qualifier:
Animals
Apoptosis / physiology*
Blotting, Western
Caspase 3 / metabolism
Cell Line, Tumor
Cytoplasm / chemistry,  metabolism*
Fluorescent Antibody Technique
Mice
Mutation
Nerve Tissue Proteins / metabolism*
Neurites / metabolism*,  pathology*
Nuclear Proteins / metabolism*
Peptides / metabolism
Transfection
Chemical
Reg. No./Substance:
0/Huntington protein, mouse; 0/Nerve Tissue Proteins; 0/Nuclear Proteins; 0/Peptides; EC 3.4.22.-/Caspase 3

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


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