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Overexpression of alpha-synuclein decreased viability and enhanced sensitivity to prostaglandin E(2), hydrogen peroxide, and a nitric oxide donor in differentiated neuroblastoma cells
- Source :
- Journal of neuroscience research. 76(3)
- Publication Year :
- 2004
-
Abstract
- Increased accumulation of alpha-synuclein is associated with certain neurodegenerative diseases including Parkinson's disease (PD) and Alzheimer's disease (AD). One mechanism of alpha-synuclein-induced toxicity involves increased oxidative stress. It was unknown whether neurons overexpressing alpha-synuclein would exhibit increased sensitivity to hydrogen peroxide (H(2)O(2)) or 3-morpholinosydnonimine (SIN-1; a nitrous oxide donor). To study this, we developed a murine neuroblastoma (NB) cell line that overexpresses wild-type human alpha-synuclein (NBP2-PN54) under the control of the cytomegalovirus (CMV) promoter using a retroviral vector. Human alpha-synuclein mRNA and protein were readily detectable in NBP2-PN54 cells. Results showed that differentiated NBP2-PN54 cells exhibited decreased viability in comparison to differentiated vector (NBP2-PN1) and parent (NBP2) control cells. These cells also exhibited increased sensitivity to PGE(2), H(2)O(2) and SIN-1. Because of involvement of proteasome inhibition in neurodegeneration, we also investigated whether treatment of differentiated NBP2-PN54 cells with PGE(2), H(2)O(2) or SIN-1 inhibits proteasome activity. Results showed that H(2)O(2) and SIN-1 inhibited proteasome activity, but PGE(2) did not. These results suggest that overexpression of alpha-synuclein not only participates directly in degeneration of neurons, but it also increases the vulnerability of neurons to other potential neurotoxins.
- Subjects :
- Cell Survival
Synucleins
Nerve Tissue Proteins
medicine.disease_cause
Transfection
Dinoprostone
Nitric oxide
Cellular and Molecular Neuroscience
chemistry.chemical_compound
Mice
Neuroblastoma
medicine
Tumor Cells, Cultured
Animals
Humans
Nitric Oxide Donors
Prostaglandin E2
Hydrogen peroxide
Alpha-synuclein
Dose-Response Relationship, Drug
Neurodegeneration
Cell Differentiation
Hydrogen Peroxide
medicine.disease
Molecular biology
nervous system
chemistry
Biochemistry
Cell culture
Molsidomine
alpha-Synuclein
Oxidative stress
medicine.drug
Subjects
Details
- ISSN :
- 03604012
- Volume :
- 76
- Issue :
- 3
- Database :
- OpenAIRE
- Journal :
- Journal of neuroscience research
- Accession number :
- edsair.doi.dedup.....0be0abfed17614583912401549fbe7da