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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
2
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pubmed:dateCreated |
2009-2-9
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pubmed:abstractText |
Parkinson's disease (PD) is a slowly progressive neurodegenerative disorder characterized by the loss of dopaminergic neurons. Dopamine is a highly toxic compound leading to generation of reactive oxygen species (ROS). DJ-1 mutations lead to early-onset inherited PD. Here, we show that DJ-1 protects against dopamine toxicity. Dopamine-exposure led to upregulation of DJ-1. Overexpression of DJ-1 increased cell resistance to dopamine toxicity and reduced intracellular ROS. Contrary effects were achieved when DJ-1 levels were reduced by siRNA. Similarly, in vivo striatal administration of 6-hydroxydopamine led to upregulation of DJ-1. Upregulation of DJ-1 was mediated by the MAP kinases pathway through activation of ERK 1, 2 in vitro and in vivo. Hence, oxidative stress, generated by free cytoplasmic dopamine, leads to upregulation of DJ-1 through the MAP kinases pathway. This mechanism elucidates how mutations in DJ-1 prompt PD and imply that modulation of DJ-1 may serve as a novel neuroprotective modality.
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
IM
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pubmed:chemical |
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pubmed:status |
MEDLINE
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pubmed:month |
Feb
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pubmed:issn |
0300-9564
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pubmed:author |
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pubmed:issnType |
Print
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pubmed:volume |
116
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
151-60
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pubmed:dateRevised |
2009-11-19
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pubmed:meshHeading |
pubmed-meshheading:18974921-Animals,
pubmed-meshheading:18974921-Blotting, Western,
pubmed-meshheading:18974921-Cell Line, Tumor,
pubmed-meshheading:18974921-Dopamine,
pubmed-meshheading:18974921-Extracellular Signal-Regulated MAP Kinases,
pubmed-meshheading:18974921-Gene Expression,
pubmed-meshheading:18974921-Humans,
pubmed-meshheading:18974921-Intracellular Signaling Peptides and Proteins,
pubmed-meshheading:18974921-Male,
pubmed-meshheading:18974921-Mice,
pubmed-meshheading:18974921-Neurons,
pubmed-meshheading:18974921-Oncogene Proteins,
pubmed-meshheading:18974921-Oxidative Stress,
pubmed-meshheading:18974921-Parkinson Disease,
pubmed-meshheading:18974921-Reactive Oxygen Species,
pubmed-meshheading:18974921-Reverse Transcriptase Polymerase Chain Reaction,
pubmed-meshheading:18974921-Transfection,
pubmed-meshheading:18974921-Up-Regulation
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pubmed:year |
2009
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pubmed:articleTitle |
DJ-1 protects against dopamine toxicity.
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pubmed:affiliation |
Department of Neurology, Felsenstein Medical Research Centre, Rabin Medical Centre, Tel Aviv University, Petah-Tikva, Israel. lev.nirit@gmail.com
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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