The Roles of Hydrogen Peroxide Exposure in the Toxic Aggregation of Alpha-synuclein and Translocation of DNA Methyltransferase-1 in Human Neuroblastoma Cell Model of Parkinson's Disease

Journal of Applied Life Sciences International

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Title The Roles of Hydrogen Peroxide Exposure in the Toxic Aggregation of Alpha-synuclein and Translocation of DNA Methyltransferase-1 in Human Neuroblastoma Cell Model of Parkinson's Disease
 
Creator Olorunyomi, O. A.
Mafulul, S. G.
Jiyil, K. M.
Smith, D. P.
 
Description Background: Oxidative stress has been implicated in neuronal damage in Parkinson’s disease (PD). However, the specific roles of reactive oxygen species such as Hydrogen peroxide (H2O2) and Iron in the pathogenesis of PD especially, alpha-synuclein (α-Syn) aggregation and translocation of nuclear DNA Methyltransferase-1(Dnmt1), are yet to be fully understood.
Aims: This study investigated and compared the effects of H2O2 and ferrous iron (Fe2+) on α-Syn aggregation and localization of Dnmt1 in human neuroblastoma cells (SH-SY5Y), using a Parkinson’s disease model expressing A53T mutation and wild typed (WT) α-Syn respectively.
Materials and Methods: The study was done using CellTox™ assay, Immunocytochemical and Enzyme-linked immunosorbent Assay (ELISA) methods. Statistical analysis of triplicate data were analysed on Microsoft Excel 2010 and Stats Direct© using one-way analysis of variance (ANOVA) and Dunnet comparison tests.
Results: Specifically, 100 µM of H2O2 caused significant reduction of cell viability, translocation of Dnmt1 from nucleus into the cytoplasm and expression of relatively higher amount of α-Syn proteins, compared to 500 µM iron after 24 hours treatment. H2O2 elicited the highest expression of both WT α-Syn (13.7 ± 0.5) ng/ml and (16.0 ± 0.2) ng/ml A53T α-Syn proteins respectively. While Iron caused the expression of (9.1± 1.1) ng/ml and (14.8 ± 1.1) ng/ml of WT and A53T α-Syn proteins respectively. The untreated controls expressed (3.2 ± 0.1) ng/ml and (7.5 ± 0.0) ng/ml of WT and A53T α-Syn proteins respectively. Furthermore, the A53T mutation also promoted the expression and aggregation of α-Syn, as evidenced with the relatively higher amount of A53T α-Syn protein compared to WT α-Syn expressed in control, H2O2 and Iron treated cells.
Conclusion: This study demonstrated that H2O2 and Fe2+ induced α-Syn aggregation and Dnmt-1 translocation, which promotes the pathogenesis of Parkinson's disease. Likewise, the A53T genetic alterations increased the overexpression and aggregation of α-Syn proteins. Hence, novel therapies targeting reactive oxygen species, oxidative stress and mutations may be beneficial for long term treatment of Parkinson’s disease.
 
Publisher SCIENCEDOMAIN international
 
Date 2020-06-09
 
Type info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
 
Format application/pdf
 
Identifier https://journaljalsi.com/index.php/JALSI/article/view/30156
10.9734/jalsi/2020/v23i430156
 
Source Journal of Applied Life Sciences International; 2020 - Volume 23 [Issue 4]; 28-44
2394-1103
 
Language eng
 
Relation https://journaljalsi.com/index.php/JALSI/article/view/30156/56588
https://journaljalsi.com/index.php/JALSI/article/view/30156/56589
 
Rights Copyright (c) 2020 © 2020 Olorunyomi et al.; This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
 

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