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Published:
Oct 5, 2018DOI:
10.4314/tjpr.v17i8.6Keywords:
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Main Article Content
Endoplasmic reticulum stress and apoptosis induced by manganese trigger α-synuclein accumulation
Abstract
Purpose: To explore whether α-synuclein aggregation is linked to endoplasmic reticulum (ER) stress and apoptosis induced by manganese (Mn) on CATH.a dopaminergic cell lines.
Methods: Western blot analysis for the expression of 78 kDa glucose-regulated protein (GRP78), phosphorylated eukaryotic initiation factor 2α (p-eIF-2α), eIF2α, inositol requiring enzyme 1(IRE-1α), cleaved caspase-3, and C/EBP homologous protein (CHOP) was performed, including overexpression of recombinant adenovirus-mediated α-synuclein on CATH.a dopaminergic cell line.
Results: It was observed that cell viability (p < 0.05) was significantly reduced by 250 μM exposed for 3h and 1,000 μM of MnCl2 exposed for 24 h. The expression of p-elF-2α, IRE-1α, and GRP78 was especially induced by 1,000 μM of MnCl2 exposed at 3, 6, and 12 h, respectively (p < 0.05). Twenty four-hour exposure of 250 uM of MnCl2 and the 3 h exposure of 1,000 uM of MnCl2 significantly induced CHOP, active caspase 3 and α-synuclein expression (p < 0.05). α-Synuclein combined with recombinant adenoviral transduction increased GRP78, IRE-1α and eIF2a, CHOP and caspase 3 expression at longer times and at higher concentrations of manganese exposure on CATH.a dopaminergic cells.
Conclusion: Based on these findings, Mn is a risk factor for diseases associated with α-synuclein accumulation. Furthermore, α-synuclein accumulation is associated with apoptosis via ER stress induced by Mn.
Keywords: Manganese (Mn), α- Synuclein, Endoplasmic reticulum (ER) stress, Apoptosis
