title: Proteome analysis reveals roles of L-DOPA in response to oxidative stress in neurons.
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.
authors.forename: Mohammad-Saeid
authors.initials: MS
authors.lastname: Jami
authors.forename: Ramavati
authors.initials: R
authors.lastname: Pal
authors.forename: Esthelle
authors.initials: E
authors.lastname: Hoedt
authors.forename: Thomas A
authors.initials: TA
authors.lastname: Neubert
authors.forename: Jan Petter
authors.initials: JP
authors.lastname: Larsen
authors.affiliation: Department of Biological Sciences, St John's University, New York, NY, USA. mollers@stjohns.edu.
authors.forename: Simon Geir
authors.initials: SG
authors.lastname: Møller
mesh_terms: D000978:Antiparkinson Agents / Q000494:pharmacology*; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects / Q000502:physiology; D003599:Cytoskeleton / Q000187:drug effects / Q000502:physiology; D015180:Electrophoresis, Gel, Two-Dimensional; D006801:Humans; D006861:Hydrogen Peroxide / Q000633:toxicity; D007980:Levodopa / Q000494:pharmacology*; D013058:Mass Spectrometry; D009474:Neurons / Q000187:drug effects* / Q000473:pathology / Q000502:physiology; D018384:Oxidative Stress / Q000187:drug effects* / Q000502:physiology; D020543:Proteome / Q000378:metabolism*; D017382:Reactive Oxygen Species / Q000378:metabolism
chemical_list: D000978:Antiparkinson Agents; D020543:Proteome; D017382:Reactive Oxygen Species; D007980:Levodopa; D006861:Hydrogen Peroxide
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