title: Survival motor neuron protein regulates apoptosis in an in vitro model of spinal muscular atrophy.
abstract: 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.
authors: Carman and Ann Adams Department of Pediatrics, Wayne State University, Detroit, MI, USA.
authors: Graham C
authors: GC
authors: Parker
authors: Xingli
authors: X
authors: Li
authors: Roumen A
authors: RA
authors: Anguelov
authors: Gabor
authors: G
authors: Toth
authors: Adam
authors: A
authors: Cristescu
authors: Gyula
authors: G
authors: Acsadi
mesh_terms: D000256:Adenoviridae / Q000235:genetics; D000818:Animals; D017209:Apoptosis / Q000502:physiology*; D053148:Caspase 3 / Q000378:metabolism; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000502:physiology; D017362:Cyclic AMP Response Element-Binding Protein / Q000235:genetics*; D066298:In Vitro Techniques; D051379:Mice; D009046:Motor Neurons / Q000166:cytology* / Q000502:physiology; D009134:Muscular Atrophy, Spinal / Q000235:genetics* / Q000473:pathology*; D009419:Nerve Tissue Proteins / Q000235:genetics*; D009447:Neuroblastoma; D034622:RNA Interference; D016601:RNA-Binding Proteins / Q000235:genetics*; D055532:SMN Complex Proteins; D013116:Spinal Cord / Q000166:cytology; D055533:Survival of Motor Neuron 1 Protein; D014162:Transfection
chemical_list: D017362:Cyclic AMP Response Element-Binding Protein; D009419:Nerve Tissue Proteins; D016601:RNA-Binding Proteins; D055532:SMN Complex Proteins; C526472:Smn1 protein, mouse; D055533:Survival of Motor Neuron 1 Protein; C505409:Casp3 protein, mouse; D053148:Caspase 3