Document Detail

Survival motor neuron protein regulates apoptosis in an in vitro model of spinal muscular atrophy.
MedLine Citation:
PMID:  18367439     Owner:  NLM     Status:  MEDLINE    
Progressive spinal muscular atrophy (SMA), the most prevalent hereditary lower motor neuron disease, is caused by mutations in the telomeric copy of the survival of motor neuron (SMN1) gene. Unlike other cells, lower motor neurons cannot tolerate low levels of smn protein. However, it is unclear as to the nature of the cell death involved. There is evidence that lower motor neurons undergo apoptosis in SMA, leading to muscle weakness and wasting. This study investigated whether SMN1 regulation in a motor neuron model affected indices of apoptotic cell death. Decreased smn expression in neuroblastoma hybrid (NSC-34) cell lines by small interfering RNA (siRNA) was demonstrated at the mRNA and protein level. Smn-depleted cells showed elevated caspase-3 activity, decreased cell viability and increased percentage of TUNEL positive cells. Conversely, NSC-34 cell smn overexpression by adenoviral gene transfer decreased staurosporine-induced caspase-3 elevation and mitigated induced cell toxicity as assessed by 3-(4,5-dimethyl thiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay. However, increased smn expression by itself did not increase cell viability. These data suggest not only that decreased smn levels increase apoptosis in an in vitro model of SMA, but also that increased smn can protect against neural injury.
Graham C Parker; Xingli Li; Roumen A Anguelov; Gabor Toth; Adam Cristescu; Gyula Acsadi
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Publication Detail:
Type:  In Vitro; Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Neurotoxicity research     Volume:  13     ISSN:  1029-8428     ISO Abbreviation:  Neurotox Res     Publication Date:  2008 Jan 
Date Detail:
Created Date:  2008-03-27     Completed Date:  2008-06-09     Revised Date:  2008-11-21    
Medline Journal Info:
Nlm Unique ID:  100929017     Medline TA:  Neurotox Res     Country:  United States    
Other Details:
Languages:  eng     Pagination:  39-48     Citation Subset:  IM    
Carman and Ann Adams Department of Pediatrics, Wayne State University, Detroit, MI, USA.
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MeSH Terms
Adenoviridae / genetics
Apoptosis / physiology*
Caspase 3 / metabolism
Cell Line, Tumor
Cell Survival / physiology
Cyclic AMP Response Element-Binding Protein / genetics*
Motor Neurons / cytology*,  physiology
Muscular Atrophy, Spinal / genetics*,  pathology*
Nerve Tissue Proteins / genetics*
RNA Interference
RNA-Binding Proteins / genetics*
SMN Complex Proteins
Spinal Cord / cytology
Survival of Motor Neuron 1 Protein
Reg. No./Substance:
0/Cyclic AMP Response Element-Binding Protein; 0/Nerve Tissue Proteins; 0/RNA-Binding Proteins; 0/SMN Complex Proteins; 0/Smn1 protein, mouse; 0/Survival of Motor Neuron 1 Protein; EC 3.4.22.-/Casp3 protein, mouse; EC 3.4.22.-/Caspase 3

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