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Dopamine Cytotoxicity on SH-SY5Y Cells: Involvement of α-Synuclein and Relevance in the Neurodegeneration of Sporadic Parkinson's Disease.
- Source :
-
Neurotoxicity research [Neurotox Res] 2019 May; Vol. 35 (4), pp. 898-907. Date of Electronic Publication: 2019 Feb 26. - Publication Year :
- 2019
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Abstract
- The cytotoxicity of dopamine on cultured cells of neural origin has been used as a tool to explore the mechanisms of dopaminergic neurodegeneration in Parkinson's disease. In the current study, we have shown that dopamine induces a dose-dependent (10-40 μM) and time-dependent (up to 96 h) loss of cell viability associated with mitochondrial dysfunction and increased intra-cellular accumulation of α-synuclein in cultured SH-SY5Y cells. Dopamine-induced mitochondrial dysfunction and the loss of cell viability under our experimental conditions could be prevented by cyclosporine, a blocker of mitochondrial permeability transition pore, as well as the antioxidant N-acetylcysteine. Interestingly, the dopamine effects on cell viability and mitochondrial functions were significantly prevented by knocking down α-synuclein expression by specific siRNA. Our results suggest that dopamine cytotoxicity is mediated by α-synuclein acting on the mitochondria and impairing its bioenergetic functions.
Details
- Language :
- English
- ISSN :
- 1476-3524
- Volume :
- 35
- Issue :
- 4
- Database :
- MEDLINE
- Journal :
- Neurotoxicity research
- Publication Type :
- Academic Journal
- Accession number :
- 30806984
- Full Text :
- https://doi.org/10.1007/s12640-019-0001-0