title: Dopamine Cytotoxicity Involves Both Oxidative and Nonoxidative Pathways in SH-SY5Y Cells: Potential Role of Alpha-Synuclein Overexpression and Proteasomal Inhibition in the Etiopathogenesis of Parkinson's Disease.
abstract: Background. The cytotoxic effects of dopamine (DA) on several catecholaminergic cell lines involve DA oxidation products like reactive oxygen species (ROS) and toxic quinones and have implications in the pathogenesis of sporadic Parkinson's disease (PD). However, many molecular details are yet to be elucidated, and the possible nonoxidative mechanism of dopamine cytotoxicity has not been studied in great detail. Results. Cultured SH-SY5Y cells treated with DA (up to 400 μM) or lactacystin (5 μM) or DA (400 μM) plus N-acetylcysteine (NAC, 2.5 mM) for 24 h are processed accordingly to observe the cell viability, mitochondrial dysfunctions, oxidative stress parameters, proteasomal activity, expression of alpha-synuclein gene, and intracellular accumulation of the protein. DA causes mitochondrial dysfunction and extensive loss of cell viability partially inhibited by NAC, potent inhibition of proteasomal activity marginally prevented by NAC, and overexpression with accumulation of intracellular alpha-synuclein partially preventable by NAC. Under similar conditions of incubation, NAC completely prevents enhanced production of ROS and increased formation of quinoprotein adducts in DA-treated SH-SY5Y cells. Separately, proteasomal inhibitor lactacystin causes accumulation of alpha-synuclein as well as mitochondrial dysfunction and cell death. Conclusions. DA cytotoxicity includes both oxidative and nonoxidative modes and may involve overexpression and accumulation of alpha-synuclein as well as proteasomal inhibition.
authors.affiliation: Department of Biochemistry, Institute of Post-Graduate Medical Education & Research, 244B, Acharya J. C. Bose Road, Kolkata 700020, India ; Department of Neuroscience, Burke-Cornell Medical Research Institute, 785 Mamaroneck Avenue, White Plains, NY 10605, USA.
authors.forename: Kalpita
authors.initials: K
authors.lastname: Banerjee
authors.affiliation: Department of Biochemistry, Institute of Post-Graduate Medical Education & Research, 244B, Acharya J. C. Bose Road, Kolkata 700020, India ; Department of Neuroscience, Rosalind Franklin University of Medicine and Science, 3333 Green Bay Road, North Chicago, IL 60064, USA.
authors.forename: Soumyabrata
authors.identifier: 0000-0001-9918-5954
authors.initials: S
authors.lastname: Munshi
authors.affiliation: Department of Biochemistry, Institute of Post-Graduate Medical Education & Research, 244B, Acharya J. C. Bose Road, Kolkata 700020, India.
authors.forename: Oishimaya
authors.initials: O
authors.lastname: Sen
authors.affiliation: DNA Laboratory, Anthropological Survey of India, 27, J. N. Road, Kolkata 700016, India.
authors.forename: Vishmadeb
authors.initials: V
authors.lastname: Pramanik
authors.affiliation: Department of Biochemistry, Institute of Post-Graduate Medical Education & Research, 244B, Acharya J. C. Bose Road, Kolkata 700020, India ; National Institute of Cholera and Enteric Diseases, P-33 C.I.T. Road, Kolkata 700010, India.
authors.forename: Tapasi
authors.initials: T
authors.lastname: Roy Mukherjee
authors.affiliation: Department of Biochemistry, Institute of Post-Graduate Medical Education & Research, 244B, Acharya J. C. Bose Road, Kolkata 700020, India.
authors.forename: Sasanka
authors.initials: S
authors.lastname: Chakrabarti