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Neurotoxicity Research

, Volume 35, Issue 4, pp 898–907 | Cite as

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

  • Upasana Ganguly
  • Anirban Ganguly
  • Oishimaya Sen
  • Gargi Ganguly
  • Roberto Cappai
  • Arghyadip Sahoo
  • Sasanka ChakrabartiEmail author
Original Article
  • 105 Downloads

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.

Keywords

α-Synuclein Dopamine Mitochondria Parkinson’s disease 

Abbreviations

PD

Parkinson’s disease

DA

Dopamine

NAC

N-Acetylcysteine

CsA

Cyclosporin A

ATP

Adenosine triphosphate

Notes

Acknowledgements

The work was supported by a research grant to Prof. Sasanka Chakrabarti from the Department of Science and Technology (DST), Government of India (No. SR/SO/HS-026/2012). Dr. Roberto Cappai received funding from the National Health and Medical Research Council (NHMRC) of Australia. Upasana Ganguly and Oishimaya Sen were supported by fellowships, respectively, from the Council of Scientific and Industrial Research (CSIR), Govt. of India (No.09/896(0012)2013-EMR-1) and the Department of Biotechnology (DBT), Govt. of India, respectively. The authors wish to thank the authority of MM (Deemed to be) University, Mullana, Ambala, Haryana, India for support. The authors also thank Mr. Vineet Kumar Khemka for assisting in statistical calculations.

Authors’ Contributions

Sasanka Chakrabarti is the principal investigator. Oishimaya Sen developed the study with guidance from Sasanka Chakrabarti and Roberto Cappai. Upasana Ganguly and Anirban Ganguly contributed equally in performing the experiments with help of Oishimaya Sen, Arghyadip Sahoo and Gargi Ganguly. Sasanka Chakrabarti analyzed the data and drafted the manuscript with help of Upasana Ganguly and Roberto Cappai. All the authors read and approved the final manuscript.

Funding Information

The work was supported by a research grant to Prof. Sasanka Chakrabarti from the Department of Science and Technology (DST), Government of India (No. SR/SO/HS-026/2012). Dr. Roberto Cappai received funding from the National Health and Medical Research Council (NHMRC), Australia. Upasana Ganguly was supported by fellowship from the Council of Scientific and Industrial Research (CSIR), Govt. of India [No. 09/896(0012)2013-EMR-1]. Oishimaya Sen was supported by fellowship from the Department of Biotechnology (DBT), Govt. of India.

Compliance with Ethical Standards

Conflict of Interest

The authors declare that they have no conflict of interest.

Supplementary material

12640_2019_1_MOESM1_ESM.doc (142 kb)
ESM 1 (DOCX 142 kb)

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Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2019

Authors and Affiliations

  • Upasana Ganguly
    • 1
  • Anirban Ganguly
    • 1
    • 2
  • Oishimaya Sen
    • 1
  • Gargi Ganguly
    • 1
  • Roberto Cappai
    • 3
  • Arghyadip Sahoo
    • 1
  • Sasanka Chakrabarti
    • 4
    Email author
  1. 1.Department of BiochemistryInstitute of Post Graduate Medical Education and ResearchKolkataIndia
  2. 2.Department of BiochemistryNil Ratan Sarkar (NRS) Medical College and HospitalKolkataIndia
  3. 3.Department of Pharmacology and Therapeutics, School of Biomedical Sciences, Faculty of Medicine, Dentistry and Health SciencesThe University of MelbourneMelbourneAustralia
  4. 4.Central Research Cell, Maharishi Markandeshwar Institute of Medical Sciences and ResearchMaharishi Markandeshwar University (Deemed to be)MullanaIndia

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