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

Jami, Mohammad-Saeid. and Pal, Ramavati. and Hoedt, Esthelle. and Neubert, Thomas.A. and Larsen, Jan Petter. and Møller, Simon Geir. (2014) Proteome analysis reveals roles of L-DOPA in response to oxidative stress in neurons. BMC Neuroscience, 15.


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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. © 2014 Jami et al.; licensee BioMed Central Ltd.

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Uncontrolled Keywords: 3 hydroxyacyl coenzyme A dehydrogenase; actin depolymerizing factor; alpha tropomyosin; cathepsin X; chaperonin 60; cofilin 1; cofilin 2; cyclophilin D; DJ 1 protein; dopamine; fumarate hydratase; glutathione; glyceraldehyde 3 phosphate dehydrogenase; hydrogen peroxide; hypoxia up regulated protein 1; levodopa; lipocortin 1; noradrenalin; nucleoside diphosphate kinase; peroxiredoxin 6; protein; reactive oxygen metabolite; reduced nicotinamide adenine dinucleotide; reduced nicotinamide adenine dinucleotide phosphate; tropomyosin alpha 1 chain; tropomyosin alpha 4 chain; unclassified drug; vimentin; levodopa; proteome; antiparkinson agent; levodopa; proteome; reactive oxygen metabolite, antioxidant activity; article; catecholamine synthesis; cell structure; cell survival; cell viability; cell viability assay; citric acid cycle; controlled study; cytoskeleton; dopaminergic nerve cell; down regulation; gene ontology; mitochondrion; neuroprotection; oxidation reduction reaction; oxidative stress; proteomics; two dimensional gel electrophoresis; upregulation; Article; drug mechanism; metabolism; nerve cell; Parkinson disease; protein analysis; drug effects; human; mass spectrometry; metabolism; nerve cell; oxidative stress; pathology; physiology; toxicity; tumor cell line, Antiparkinson Agents; Cell Line, Tumor; Cell Survival; Cytoskeleton; Electrophoresis, Gel, Two-Dimensional; Humans; Hydrogen Peroxide; Levodopa; Mass Spectrometry; Neurons; Oxidative Stress; Proteome; Reactive Oxygen Species
Subjects: WL Nervous system
QU Biochemistry
Divisions: Faculty of Medicine
Depositing User: zahra bagheri .
Date Deposited: 01 Aug 2017 03:38
Last Modified: 04 Mar 2018 06:44

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