Overexpression of alpha-synuclein decreased viability and enhanced sensitivity to prostaglandin E(2), hydrogen peroxide, and a nitric oxide donor in differentiated neuroblastoma cells
Autor: | Kedar N. Prasad, Judith E. Prasad, Xiang Dong Yan, Amy J. Hanson, Cynthia Andreatta, Bipin Kumar, Piruz Nahreini |
---|---|
Rok vydání: | 2004 |
Předmět: |
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 |
Zdroj: | Journal of neuroscience research. 76(3) |
ISSN: | 0360-4012 |
Popis: | 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. |
Databáze: | OpenAIRE |
Externí odkaz: |