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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.
J Neurosci Res. 2004 May 01; 76(3):415-22.JN

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.

Authors+Show Affiliations

Prasad JE
Center for Vitamins and Cancer Research, Department of Radiology, School of Medicine, University of Colorado Health Sciences Center, Denver 80262, USA.
Kumar B
No affiliation info available
Andreatta C
No affiliation info available
Nahreini P
No affiliation info available
Hanson AJ
No affiliation info available
Yan XD
No affiliation info available
Prasad KN
No affiliation info available

MeSH

AnimalsCell DifferentiationCell SurvivalDinoprostoneDose-Response Relationship, DrugHumansHydrogen PeroxideMiceMolsidomineNerve Tissue ProteinsNeuroblastomaNitric Oxide DonorsSynucleinsTransfectionTumor Cells, Culturedalpha-Synuclein

Pub Type(s)

Comparative Study
Journal Article
Research Support, U.S. Gov't, P.H.S.

Language

eng

PubMed ID

15079871

Citation

Prasad, Judith E., et al. "Overexpression of Alpha-synuclein Decreased Viability and Enhanced Sensitivity to Prostaglandin E(2), Hydrogen Peroxide, and a Nitric Oxide Donor in Differentiated Neuroblastoma Cells." Journal of Neuroscience Research, vol. 76, no. 3, 2004, pp. 415-22.
Prasad JE, Kumar B, Andreatta C, et al. Overexpression of alpha-synuclein decreased viability and enhanced sensitivity to prostaglandin E(2), hydrogen peroxide, and a nitric oxide donor in differentiated neuroblastoma cells. J Neurosci Res. 2004;76(3):415-22.
Prasad, J. E., Kumar, B., Andreatta, C., Nahreini, P., Hanson, A. J., Yan, X. D., & Prasad, K. N. (2004). Overexpression of alpha-synuclein decreased viability and enhanced sensitivity to prostaglandin E(2), hydrogen peroxide, and a nitric oxide donor in differentiated neuroblastoma cells. Journal of Neuroscience Research, 76(3), 415-22.
Prasad JE, et al. Overexpression of Alpha-synuclein Decreased Viability and Enhanced Sensitivity to Prostaglandin E(2), Hydrogen Peroxide, and a Nitric Oxide Donor in Differentiated Neuroblastoma Cells. J Neurosci Res. 2004 May 1;76(3):415-22. PubMed PMID: 15079871.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Overexpression of alpha-synuclein decreased viability and enhanced sensitivity to prostaglandin E(2), hydrogen peroxide, and a nitric oxide donor in differentiated neuroblastoma cells. AU - Prasad,Judith E, AU - Kumar,Bipin, AU - Andreatta,Cynthia, AU - Nahreini,Piruz, AU - Hanson,Amy J, AU - Yan,Xiang Dong, AU - Prasad,Kedar N, PY - 2004/4/14/pubmed PY - 2004/7/30/medline PY - 2004/4/14/entrez SP - 415 EP - 22 JF - Journal of neuroscience research JO - J Neurosci Res VL - 76 IS - 3 N2 - 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. SN - 0360-4012 UR - https://www.unboundmedicine.com/medline/citation/15079871/Overexpression_of_alpha_synuclein_decreased_viability_and_enhanced_sensitivity_to_prostaglandin_E_2__hydrogen_peroxide_and_a_nitric_oxide_donor_in_differentiated_neuroblastoma_cells_ DB - PRIME DP - Unbound Medicine ER -