title: Different expression levels of spartin cause broad spectrum of cellular consequences in human neuroblastoma cells.
abstract: Hereditary spastic paraplegia describes a diverse group of neurodegenerative conditions characterised by progressive spasticity and weakness of the lower limbs. Mutations in the SPG20 gene encoding spartin cause an autosomal recessive hereditary spastic paraplegia known as Troyer syndrome. To evaluate the cellular consequences of sustained spartin depletion in neuronal cells, we established several clonal SH-SY5Y cell lines with different level of spartin knockdown. Here, we report that cells with modest spartin downregulation show signs of neuronal differentiation such as increased neuritogenesis and cytoskeleton rearrangement. Interestingly, we also indicate that permanent high level spartin depletion results in impaired cell growth and multiple mitochondrial aberrations, which we speculate, arise as a result of chronic oxidative stress. Our studies demonstrate that the scale of spartin downregulation is the major factor that determines the severity of cellular consequences observed and suggest that there is a critical level of spartin expression which must be maintained for proper cellular functions.
authors.affiliation: School of Medicine and Medical Science, Conway Institute of Biomolecular and Biomedical Research, University College Dublin, Belfield, Dublin 4, Ireland.
authors.forename: Malgorzata
authors.initials: M
authors.lastname: Milewska
authors.affiliation: School of Medicine and Medical Science, Conway Institute of Biomolecular and Biomedical Research, University College Dublin, Belfield, Dublin 4, Ireland.
authors.forename: Paula Catherine
authors.initials: PC
authors.lastname: Byrne
mesh_terms: D018797:Cell Cycle Proteins; D045744:Cell Line, Tumor; D004305:Dose-Response Relationship, Drug; D015536:Down-Regulation; D015870:Gene Expression / Q000187:drug effects; D055785:Gene Knockdown Techniques; D006801:Humans; D008928:Mitochondria / Q000378:metabolism; D009447:Neuroblastoma / Q000378:metabolism* / Q000473:pathology*; D018384:Oxidative Stress / Q000502:physiology; D011506:Proteins / Q000235:genetics / Q000378:metabolism*; D015419:Spastic Paraplegia, Hereditary / Q000235:genetics
chemical_list: D018797:Cell Cycle Proteins; D011506:Proteins; C464787:SPART protein, human
keywords: Troyer syndrome; live cell imaging; mitochondria; neuroblastoma cells; oxidative stress; spartin