Overexpression of α-synuclein decreased viability and enhanced sensitivity to prostaglandin E2, hydrogen peroxide, and a nitric oxide donor in differentiated neuroblastoma cells

✍ Scribed by Judith E. Prasad; Bipin Kumar; Cynthia Andreatta; Piruz Nahreini; Amy J. Hanson; Xiang Dong Yan; Kedar N. Prasad

• Publisher: John Wiley and Sons
• Year: 2004
• Tongue: English
• Weight: 288 KB
• Volume: 76
• Category: Article
• ISSN: 0360-4012
• DOI: 10.1002/jnr.20058

✦ Synopsis

Increased accumulation of ␣-synuclein is associated with certain neurodegenerative diseases including Parkinson's disease (PD) and Alzheimer's disease (AD). One mechanism of ␣-synuclein-induced toxicity involves increased oxidative stress. It was unknown whether neurons overexpressing ␣-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 ␣-synuclein (NBP2-PN54) under the control of the cytomegalovirus (CMV) promoter using a retroviral vector. Human ␣-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 ␣-synuclein not only participates directly in degeneration of neurons, but it also increases the vulnerability of neurons to other potential neurotoxins.