| pubmed-article:11588178 | rdf:type | pubmed:Citation | lld:pubmed |
| pubmed-article:11588178 | lifeskim:mentions | umls-concept:C0178719 | lld:lifeskim |
| pubmed-article:11588178 | lifeskim:mentions | umls-concept:C0285890 | lld:lifeskim |
| pubmed-article:11588178 | lifeskim:mentions | umls-concept:C0332621 | lld:lifeskim |
| pubmed-article:11588178 | lifeskim:mentions | umls-concept:C0205263 | lld:lifeskim |
| pubmed-article:11588178 | pubmed:issue | 20 | lld:pubmed |
| pubmed-article:11588178 | pubmed:dateCreated | 2001-10-5 | lld:pubmed |
| pubmed-article:11588178 | pubmed:abstractText | Brain lesions containing filamentous and aggregated alpha-synuclein are hallmarks of neurodegenerative synucleinopathies. Oxidative stress has been implicated in the formation of these lesions. Using HEK 293 cells stably transfected with wild-type and mutant alpha-synuclein, we demonstrated that intracellular generation of nitrating agents results in the formation of alpha-synuclein aggregates. Cells were exposed simultaneously to nitric oxide- and superoxide-generating compounds, and the intracellular formation of peroxynitrite was demonstrated by monitoring the oxidation of dihydrorhodamine 123 and the nitration of alpha-synuclein. Light microscopy using antibodies against alpha-synuclein and electron microscopy revealed the presence of perinuclear aggregates under conditions in which peroxynitrite was generated but not when cells were exposed to nitric oxide- or superoxide-generating compounds separately. alpha-Synuclein aggregates were observed in 20-30% of cells expressing wild-type or A53T mutant alpha-synuclein and in 5% of cells expressing A30P mutant alpha-synuclein. No evidence of synuclein aggregation was observed in untransfected cells or cells expressing beta-synuclein. In contrast, selective inhibition of the proteasome resulted in the formation of aggregates detected with antibodies to ubiquitin in the majority of the untransfected cells and cells expressing alpha-synuclein. However, alpha-synuclein did not colocalize with these aggregates, indicating that inhibition of the proteasome does not promote alpha-synuclein aggregation. In addition, proteasome inhibition did not alter the steady-state levels of alpha-synuclein, but addition of the lysosomotropic agent ammonium chloride significantly increased the amount of alpha-synuclein, indicating that lysosomes are involved in degradation of alpha-synuclein. Our data indicate that nitrative and oxidative insult may initiate pathogenesis of alpha-synuclein aggregates. | lld:pubmed |
| pubmed-article:11588178 | pubmed:language | eng | lld:pubmed |
| pubmed-article:11588178 | pubmed:journal | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:11588178 | pubmed:citationSubset | IM | lld:pubmed |
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| pubmed-article:11588178 | pubmed:status | MEDLINE | lld:pubmed |
| pubmed-article:11588178 | pubmed:month | Oct | lld:pubmed |
| pubmed-article:11588178 | pubmed:issn | 1529-2401 | lld:pubmed |
| pubmed-article:11588178 | pubmed:author | pubmed-author:PaxinosGG | lld:pubmed |
| pubmed-article:11588178 | pubmed:author | pubmed-author:TrojanowskiJ... | lld:pubmed |
| pubmed-article:11588178 | pubmed:author | pubmed-author:ChewHH | lld:pubmed |
| pubmed-article:11588178 | pubmed:author | pubmed-author:LeeV MVM | lld:pubmed |
| pubmed-article:11588178 | pubmed:author | pubmed-author:Ischiropoulos... | lld:pubmed |
| pubmed-article:11588178 | pubmed:author | pubmed-author:RueterS MSM | lld:pubmed |
| pubmed-article:11588178 | pubmed:author | pubmed-author:WeisseMM | lld:pubmed |
| pubmed-article:11588178 | pubmed:author | pubmed-author:GiassonB IBI | lld:pubmed |
| pubmed-article:11588178 | pubmed:author | pubmed-author:NorrisE HEH | lld:pubmed |
| pubmed-article:11588178 | pubmed:issnType | Electronic | lld:pubmed |
| pubmed-article:11588178 | pubmed:day | 15 | lld:pubmed |
| pubmed-article:11588178 | pubmed:volume | 21 | lld:pubmed |
| pubmed-article:11588178 | pubmed:owner | NLM | lld:pubmed |
| pubmed-article:11588178 | pubmed:authorsComplete | Y | lld:pubmed |
| pubmed-article:11588178 | pubmed:pagination | 8053-61 | lld:pubmed |
| pubmed-article:11588178 | pubmed:dateRevised | 2006-11-15 | lld:pubmed |
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| pubmed-article:11588178 | pubmed:year | 2001 | lld:pubmed |
| pubmed-article:11588178 | pubmed:articleTitle | Induction of alpha-synuclein aggregation by intracellular nitrative insult. | lld:pubmed |
| pubmed-article:11588178 | pubmed:affiliation | Stokes Research Institute and Department of Biochemistry and Biophysics, Children's Hospital of Philadelphia and The University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA. | lld:pubmed |
| pubmed-article:11588178 | pubmed:publicationType | Journal Article | lld:pubmed |
| pubmed-article:11588178 | pubmed:publicationType | Research Support, U.S. Gov't, P.H.S. | lld:pubmed |
| pubmed-article:11588178 | pubmed:publicationType | Research Support, Non-U.S. Gov't | lld:pubmed |
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