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alpha-Synuclein overexpression during manganese-induced apoptosis in SH-SY5Y neuroblastoma cells
Yan Li1, Liguang Sun, Tongjian Cai
1Department of Biochemical and Molecular Biology, China Medical University, Shenyang City 110001, Liaoning Province, China.
Abstract:
Chronic inorganic manganese (Mn) exposure has been known to induce neurological disorders similar to Parkinson's disease (PD). Apoptosis has been shown to be involved in manganese-induced neurotoxicity. However, the up-stream molecular mechanisms for cell apoptosis are not established. alpha-Synuclein (alpha-syn) is a major component of intracellular inclusions in PD, Alzheimer's disease (AD), and other neurodegenerative disorders. We investigated the role of alpha-syn in manganese chloride (MnCl(2))-induced apoptosis. Results show that MnCl(2) enhanced transcriptional and translational alpha-syn overexpression, and apoptosis as measured by caspase-3 activity and flow cytometry. Overexpressing alpha-syn exacerbated manganese-induced apoptosis, whereas antisense alpha-syn treatment significantly reversed MnCl(2)-induced apoptosis in human neuroblastoma SH-SY5Y cells. In conclusion, our results imply that intracellular alpha-syn overexpression may be responsible for MnCl(2)-induced apoptosis.
Insights
Chronic manganese exposure causes neurotoxicity. This study reveals that alpha-synuclein (alpha-syn) overexpression is a key factor in manganese-induced apoptosis, a cell death pathway implicated in neurodegenerative diseases.
Area of Science:
- Neuroscience
- Toxicology
- Cell Biology
Background:
- Chronic inorganic manganese (Mn) exposure is linked to neurological disorders resembling Parkinson's disease (PD).
- Apoptosis (programmed cell death) is implicated in manganese-induced neurotoxicity, but upstream molecular triggers remain unclear.
- Alpha-synuclein (alpha-syn) is a critical protein found in cellular inclusions characteristic of PD and other neurodegenerative diseases.
Purpose of the Study:
- To investigate the role of alpha-synuclein (alpha-syn) in manganese chloride (MnCl2)-induced apoptosis.
- To elucidate the molecular mechanisms underlying manganese neurotoxicity.
Main Methods:
- Utilized human neuroblastoma SH-SY5Y cells.
- Assessed MnCl2-induced apoptosis using caspase-3 activity assays and flow cytometry.
- Manipulated alpha-syn expression levels via overexpression and antisense treatments.
Main Results:
- MnCl2 exposure led to increased alpha-synuclein (alpha-syn) expression at both transcriptional and translational levels.
- MnCl2 exposure significantly increased apoptosis.
- Overexpression of alpha-syn exacerbated MnCl2-induced apoptosis.
- Antisense-mediated reduction of alpha-syn reversed MnCl2-induced apoptosis.
Conclusions:
- Intracellular alpha-synuclein (alpha-syn) overexpression plays a significant role in manganese chloride (MnCl2)-induced apoptosis.
- Alpha-synuclein may be a critical mediator of manganese neurotoxicity.
- Targeting alpha-synuclein could offer a therapeutic strategy for manganese-induced neurotoxicity.
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