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

Jami MS, Pal R, Hoedt E, Neubert TA, Larsen JP, Møller SG - BMC Neurosci (2014)

Bottom Line: 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.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.

View Article: PubMed Central - PubMed

Affiliation: Department of Biological Sciences, St John's University, New York, NY, USA. mollers@stjohns.edu.

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.

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Related in: MedlinePlus

Close-up view of protein spots differentially represented in response to H2O2, L-DOPA and H2O2/L-DOPA treatments. Enlargements of gel portions containing the differentially abundant protein spots indicated in the gels shown in Figures 2 and 3. Column charts show the ratio for each differentially expressed protein. Differentially expressed proteins were studied using Student's t-test. The relative spot volume (Vol%) for proteins from the control condition was set to “1”.
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Fig4: Close-up view of protein spots differentially represented in response to H2O2, L-DOPA and H2O2/L-DOPA treatments. Enlargements of gel portions containing the differentially abundant protein spots indicated in the gels shown in Figures 2 and 3. Column charts show the ratio for each differentially expressed protein. Differentially expressed proteins were studied using Student's t-test. The relative spot volume (Vol%) for proteins from the control condition was set to “1”.

Mentions: We studied and classified the differentially expressed proteins according to their gene ontology (GO, with focus on biological process) through Uniprot (protein knowledge website: http://www.uniprot.org/) and QuickGO (http://www.ebi.ac.uk/QuickGO/). Several biological processes and pathways were affected due to the treatment conditions. For instance the majority of protein changes in response to oxidative stress belong to the “cell motion (GO:0006928)” category, most of which were reversed by L-DOPA co-treatment. More detailed information regarding the differentially expressed proteins are illustrated in Figure 4, summarized in Table 2 and discussed below.Figure 4


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

Jami MS, Pal R, Hoedt E, Neubert TA, Larsen JP, Møller SG - BMC Neurosci (2014)

Close-up view of protein spots differentially represented in response to H2O2, L-DOPA and H2O2/L-DOPA treatments. Enlargements of gel portions containing the differentially abundant protein spots indicated in the gels shown in Figures 2 and 3. Column charts show the ratio for each differentially expressed protein. Differentially expressed proteins were studied using Student's t-test. The relative spot volume (Vol%) for proteins from the control condition was set to “1”.
© Copyright Policy - open-access
Related In: Results  -  Collection

License 1 - License 2
Show All Figures
getmorefigures.php?uid=PMC4125692&req=5

Fig4: Close-up view of protein spots differentially represented in response to H2O2, L-DOPA and H2O2/L-DOPA treatments. Enlargements of gel portions containing the differentially abundant protein spots indicated in the gels shown in Figures 2 and 3. Column charts show the ratio for each differentially expressed protein. Differentially expressed proteins were studied using Student's t-test. The relative spot volume (Vol%) for proteins from the control condition was set to “1”.
Mentions: We studied and classified the differentially expressed proteins according to their gene ontology (GO, with focus on biological process) through Uniprot (protein knowledge website: http://www.uniprot.org/) and QuickGO (http://www.ebi.ac.uk/QuickGO/). Several biological processes and pathways were affected due to the treatment conditions. For instance the majority of protein changes in response to oxidative stress belong to the “cell motion (GO:0006928)” category, most of which were reversed by L-DOPA co-treatment. More detailed information regarding the differentially expressed proteins are illustrated in Figure 4, summarized in Table 2 and discussed below.Figure 4

Bottom Line: 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.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.

View Article: PubMed Central - PubMed

Affiliation: Department of Biological Sciences, St John's University, New York, NY, USA. mollers@stjohns.edu.

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.

Show MeSH
Related in: MedlinePlus