Source:http://linkedlifedata.com/resource/pubmed/id/19697948
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rdf:type | |
lifeskim:mentions | |
pubmed:issue |
18
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pubmed:dateCreated |
2009-9-14
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pubmed:abstractText |
Alpha-synuclein is a major component of Lewy bodies, proteinacious inclusions which are a major hallmark of Parkinson's disease (PD). Lewy bodies contain high levels of nitrated tyrosine residues as determined by antibodies specific for 3-nitrotyrosine (3NT) and via mass spectrometry (MS). We have developed a multiple reaction monitoring (MRM) mass spectrometry method to sensitively quantitate the 3NT levels of specific alpha-synuclein tyrosine residues. We found a 9-fold increase (relative to controls) in levels of 3NT at Tyr-39 of alpha-synuclein in an inducible transgenic cellular model of Parkinson's disease in which monoamine oxidase B (MAO-B) is overexpressed and which emulates several features of PD. Increased nitration of Tyr-39 on endogenous alpha-synuclein via elevations in MAO-B levels could be abrogated by the addition of deprenyl, a specific MAO-B inhibitor. The increased levels of 3NT was selective for Tyr-39 as no significant increases in 3NT levels were detected at other tyrosine residues present in the protein (Tyr-125, Tyr-133, and Tyr-136). This is the first report of increased 3NT levels of a specific tyrosine in a PD model and the first use of MRM mass spectrometry to quantify changes in 3NT modifications at specific sites within a target protein.
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pubmed:grant |
http://linkedlifedata.com/resource/pubmed/grant/P01 AG025901-01A2,
http://linkedlifedata.com/resource/pubmed/grant/P30 AG025708,
http://linkedlifedata.com/resource/pubmed/grant/P30 AG025708-059004,
http://linkedlifedata.com/resource/pubmed/grant/PL1 AG032118,
http://linkedlifedata.com/resource/pubmed/grant/PL1 AG032118-03,
http://linkedlifedata.com/resource/pubmed/grant/R01 AG030232-01,
http://linkedlifedata.com/resource/pubmed/grant/RL1 NS062415,
http://linkedlifedata.com/resource/pubmed/grant/RL1 NS062415-03
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pubmed:language |
eng
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pubmed:journal | |
pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/3-nitrotyrosine,
http://linkedlifedata.com/resource/pubmed/chemical/Monoamine Oxidase,
http://linkedlifedata.com/resource/pubmed/chemical/Nitrates,
http://linkedlifedata.com/resource/pubmed/chemical/Tyrosine,
http://linkedlifedata.com/resource/pubmed/chemical/alpha-Synuclein
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pubmed:status |
MEDLINE
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pubmed:month |
Sep
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pubmed:issn |
1520-6882
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pubmed:author | |
pubmed:issnType |
Electronic
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pubmed:day |
15
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pubmed:volume |
81
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
7823-8
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pubmed:dateRevised |
2011-5-6
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pubmed:meshHeading |
pubmed-meshheading:19697948-Animals,
pubmed-meshheading:19697948-Lewy Bodies,
pubmed-meshheading:19697948-Mass Spectrometry,
pubmed-meshheading:19697948-Models, Biological,
pubmed-meshheading:19697948-Monoamine Oxidase,
pubmed-meshheading:19697948-Nitrates,
pubmed-meshheading:19697948-Oxidative Stress,
pubmed-meshheading:19697948-PC12 Cells,
pubmed-meshheading:19697948-Parkinson Disease,
pubmed-meshheading:19697948-Rats,
pubmed-meshheading:19697948-Tyrosine,
pubmed-meshheading:19697948-alpha-Synuclein
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pubmed:year |
2009
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pubmed:articleTitle |
Preferentially increased nitration of alpha-synuclein at tyrosine-39 in a cellular oxidative model of Parkinson's disease.
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pubmed:affiliation |
Buck Institute for Age Research, 8001 Redwood Boulevard, Novato, California 94945, USA.
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pubmed:publicationType |
Journal Article,
Research Support, N.I.H., Extramural
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