6‑Hydroxydopamine induces neurodegeneration in terminally differentiated SH‑SY5Y neuroblastoma cells via enrichment of the nucleosomal degradation pathway: a global proteomics approach

Magalingam, Kasthuri, Somanath, Sushela Devi, Ramdas, Premdass, Nagaraja, Haleagrahara, and Radhakrishnan, Ammu (2022) 6‑Hydroxydopamine induces neurodegeneration in terminally differentiated SH‑SY5Y neuroblastoma cells via enrichment of the nucleosomal degradation pathway: a global proteomics approach. Journal of Molecular Neuroscience, 72. pp. 1026-1046.

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Abstract

The SH-SY5Y human neuroblastoma cells have been used for decades as a cell-based model of dopaminergic neurons to explore the underlying science of cellular and molecular mechanisms of neurodegeneration in Parkinson’s disease (PD). However, data revealing the protein expression changes in 6-OHDA induced cytotoxicity in differentiated SH-SY5Y cells remain void. Therefore, we investigated the differentially regulated proteins expressed in terminally differentiated SH-SY5Y cells (differ-SH-SY5Y neural cells) exposed to 6-hydroxydopamine (6-OHDA) using the LC–MS/MS technology and construed the data using the online bioinformatics databases such as PANTHER, STRING, and KEGG. Our studies demonstrated that the neuronal development in differ-SH-SY5Y neural cells was indicated by the overexpression of proteins responsible for neurite formations such as calnexin (CANX) and calreticulin (CALR) besides significant downregulation of ribosomal proteins. The enrichment of the KEGG ribosome pathway was detected with significant downregulation (p < 0.05) of all the 21 ribosomal proteins in differ-SH-SY5Y neural cells compared with undifferentiated cells. Whereas in the PD model, the pathological changes induced by 6-OHDA were indicated by the presence of unfolded and misfolded proteins, which triggered the response of 10 kDa heat shock proteins (HSP), namely HSPE1 and HSPA9. Moreover, the 6-OHDA-induced neurodegeneration in differ-SH-SY5Y neural cells also upregulated the voltage-dependent anion-selective channel protein 1 (VDAC1) protein and enriched the KEGG systemic lupus erythematosus (SLE) pathway that was regulated by 17 histone proteins (p < 0.05) in differ-SH-SY5Y neural cells. These results suggest that the nucleosomal degradation pathway may have regulated the 6-OHDA induced neurodegeneration in PD cell-based model, which is reflected by increased apoptosis and histone release in differ-SH-SY5Y neural cells.

Item ID: 73222
Item Type: Article (Research - C1)
ISSN: 1559-1166
Keywords: Parkinson’s disease (PD), 6-Hydroxydopamine (6-OHDA), Human neuroblastoma cells (SH-SY5Y)
Copyright Information: © The Author(s) 2022 This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/.
Date Deposited: 30 Mar 2022 00:33
FoR Codes: 32 BIOMEDICAL AND CLINICAL SCIENCES > 3209 Neurosciences > 320903 Central nervous system @ 100%
SEO Codes: 20 HEALTH > 2001 Clinical health > 200101 Diagnosis of human diseases and conditions @ 100%
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