Dopamine Cytotoxicity on SH-SY5Y Cells: Involvement of α-Synuclein and Relevance in the Neurodegeneration of Sporadic Parkinson's Disease

Neurotoxicity Research
Upasana GangulySasanka Chakrabarti

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.

References

Nov 21, 2000·Free Radical Biology & Medicine·J N KellerW F Maragos
Nov 25, 2000·Toxicology·A Nicotra, S H Parvez
Apr 30, 2003·The Journal of Biological Chemistry·Julie L WebbDavid C Rubinsztein
Apr 3, 2004·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Jie LiAnthony L Fink
Sep 29, 2004·Lancet·Marie-Christine Chartier-HarlinAlain Destée
Oct 27, 2004·Cell and Tissue Research·Andreas Schober
Apr 9, 2005·The Journal of Biological Chemistry·Erin H NorrisVirginia M-Y Lee
Jun 11, 2005·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Roberto CappaiAndrew F Hill
Sep 29, 2006·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Joseph R MazzulliHarry Ischiropoulos
Oct 5, 2006·Journal of Neural Transmission. Supplementum·W MaruyamaM Naoi
Sep 6, 2007·The Journal of Biological Chemistry·Joseph R MazzulliHarry Ischiropoulos
Oct 30, 2007·Acta Neuropathologica·William J BurkeJames E Galvin
Jan 11, 2008·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Linan ChenXiaoxi Zhuang
Mar 3, 2009·Free Radical Biology & Medicine·Su Ling LeongRoberto Cappai
Mar 18, 2009·Free Radical Research·Zhi Dong Zhou, Tit Meng Lim
May 16, 2009·Neurochemical Research·Su Ling LeongChi Le Lan Pham
Sep 5, 2009·Trends in Pharmacological Sciences·Francesca CicchettiRobert E Gross
Dec 8, 2009·Journal of Bioenergetics and Biomembranes·Teresa G Hastings
Jan 15, 2011·Parkinson's Disease·Darcy LitteljohnShawn Hayley
Jan 15, 2011·Parkinson's Disease·Shin Hisahara, Shun Shimohama
Oct 26, 2011·Biochimica Et Biophysica Acta·Leonid BreydoVladimir N Uversky
May 26, 2012·Neurotoxicology·Carmen Freire, Sergio Koifman
Aug 4, 2012·ACS Chemical Neuroscience·Tiffiny ChanKagan Kerman
Dec 21, 2012·Nature Reviews. Neuroscience·Hilal A LashuelEliezer Masliah
Aug 27, 2013·Methods in Molecular Biology·Jane Kovalevich, Dianne Langford
Jan 31, 2015·Toxicological Sciences : an Official Journal of the Society of Toxicology·Patricia MuñozJuan Segura-Aguilar
May 20, 2016·Neuron·Patrick P MichelStéphane Hunot
Jun 10, 2016·Science Translational Medicine·Roberto Di MaioJ Timothy Greenamyre
Dec 1, 2017·Current Neuropharmacology·Upasana GangulySasanka Chakrabarti
Oct 22, 2018·Neurotoxicity Research·Sandro HuenchugualaJuan Segura-Aguilar

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Citations

Nov 30, 2019·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Isabella BologninoMarco Catto
Apr 15, 2020·International Journal of Molecular Sciences·Francesca OppedisanoVincenzo Mollace
Feb 14, 2021·Journal of Chemical Neuroanatomy·Xiaohong WangXinqing Guo
Jul 31, 2021·Journal of Cellular and Molecular Medicine·Aimee Rodica ChisMihaela Simu

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Methods Mentioned

BETA
transgenic
transfection
electrophoresis
PCR
gene knock-down

Software Mentioned

Syngene Gene Tools

Related Concepts

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Alpha-Synuclein Aggregation (MDS)

Alpha-synucleins are small proteins that are believed to restrict the mobility of synpatic vesicles and inhibit neurotransmitter release. Aggregation of these proteins have been linked to several types of neurodegenerative diseases including dementia with Lewy bodies and Parkinson's disease. Here is the latest research on α-synuclein aggregation.