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Open Access Highly Accessed Research article

Proteome analysis reveals roles of L-DOPA in response to oxidative stress in neurons

Mohammad-Saeid Jami14, Ramavati Pal1, Esthelle Hoedt2, Thomas A Neubert2, Jan Petter Larsen3 and Simon Geir Møller13*

Author Affiliations

1 Department of Biological Sciences, St John’s University, New York, NY, USA

2 Kimmel Center for Biology and Medicine at the Skirball Institute and Department of Biochemistry and Molecular Pharmacology, New York University School of Medicine, New York, NY, USA

3 The Norwegian Centre for Movement Disorders, Stavanger University Hospital, Stavanger, Norway

4 Cellular and Molecular Research Center, School of Medicine, Shahrekord University of Medical Sciences, Shahrekord, Iran

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BMC Neuroscience 2014, 15:93  doi:10.1186/1471-2202-15-93

Published: 31 July 2014

Abstract

Background

Parkinson’s disease (PD) is the second most common neurodegenerative movement disorder, caused by preferential dopaminergic neuronal cell death in the substantia nigra, a process also influenced by oxidative stress. L-3,4-dihydroxyphenylalanine (L-DOPA) represents the main treatment route for motor symptoms associated with PD however, its exact mode of action remains unclear. A spectrum of conflicting data suggests that L-DOPA may damage dopaminergic neurons due to oxidative stress whilst other data suggest that L-DOPA itself may induce low levels of oxidative stress, which in turn stimulates endogenous antioxidant mechanisms and neuroprotection.

Results

In this study we performed a two-dimensional gel electrophoresis (2DE)-based proteomic study to gain further insight into the mechanism by which L-DOPA can influence the toxic effects of H2O2 in neuronal cells. We observed that oxidative stress affects metabolic pathways as well as cytoskeletal integrity and that neuronal cells respond to oxidative conditions by enhancing numerous survival pathways. Our study underlines the complex nature of L-DOPA in PD and sheds light on the interplay between oxidative stress and L-DOPA.

Conclusions

Oxidative stress changes neuronal metabolic routes and affects cytoskeletal integrity. Further, L-DOPA appears to reverse some H2O2-mediated effects evident at both the proteome and cellular level.

Keywords:
Parkinson’s disease; Oxidative stress; Dopamine; Proteomics