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.
Highlights
Over the last 20 years, a significant amount of data has emerged suggesting different cellular models that are valuable in evaluating potential drug targets in modulating1 3 the disease course in Parkinson’s disease (PD)
When we compared the standard protein sets between differentiated and undifferentiated SH-SY5Y neural cells, we found a total of 189 (Table 1) common proteins appeared in both protein data sets with
The SH-SY5Y human neuroblastoma cell line is regarded as versatile neuronal cells that can be applied in multitude neuroscience research
Summary
Over the last 20 years, a significant amount of data has emerged suggesting different cellular models that are valuable in evaluating potential drug targets in modulating1 3 the disease course in PD. Whether undifferentiated or differentiated SH-SY5Y neuroblastoma should be used as a substitute to dopaminergic neurons in PD-related studies remain controversial. Most neuroscience researchers have suggested that it is of great importance to utilize the differentiated SH-SY5Y human neuroblastoma cells that resemble human dopamine neurons for PD studies (Magalingam et al 2020). Our previous studies have delineated that the RA-induced differentiation on SHSY5Y cells in a low-serum culture medium demonstrated enhanced neurite projection with longer varicosities connecting the adjacent cells, reduced proliferation rate as well as increased levels of dopamine and alpha-synuclein. Our findings correlate with numerous previous studies that suggested that differentiated SH-SY5Y cell line possesses the closest resemblance with dopaminergic cells and is suitable for neurodegenerative related studies (Khwanraj et al 2015; Lopes et al 2017)
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