| Phosphorylated IkappaBalpha is a component of Lewy body of Parkinson's disease. | |
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MedLine Citation:
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PMID: 15845394 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Ubiquitin is one of the major components of Lewy bodies (LB), the pathological hallmark of Parkinson's disease (PD). Here, we identified that a phosphorylated form of IkappaBalpha (pIkappaBalpha), an inhibitor of NF-kappaB, and SCF(beta-TrCP), the ubiquitin ligase of pIkappaBalpha, are components of LB in brains of PD patients. In vitro studies identified those proteins in the ubiquitin- and alpha-synuclein (known as the major component of LB)-positive LB-like inclusions generated in dopaminergic SH-SY5Y cells treated with MG132, a proteasome inhibitor. Intriguingly, IkappaBalpha migration into such ubiquitinated inclusions in cells treated with MG132 was inhibited by a cell-permeable peptide known to block phosphorylation of IkappaBalpha, although this peptide did not influence cell viability under proteasomal inhibition. Our results indicate that phosphorylation of IkappaBalpha plays a role in the formation of IkappaBalpha-containing inclusions caused by proteasomal dysfunction, and that the generation of such inclusion is independent of cell death caused by impairment of proteasome. |
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Authors:
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Kazuyuki Noda; Toshiaki Kitami; Wei Ping Gai; Fariba Chegini; Poul Henning Jensen; Tsutomu Fujimura; Kimie Murayama; Keiji Tanaka; Yoshikuni Mizuno; Nobutaka Hattori |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't |
Journal Detail:
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Title: Biochemical and biophysical research communications Volume: 331 ISSN: 0006-291X ISO Abbreviation: Biochem. Biophys. Res. Commun. Publication Date: 2005 May |
Date Detail:
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Created Date: 2005-04-22 Completed Date: 2005-06-28 Revised Date: 2006-11-15 |
Medline Journal Info:
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Nlm Unique ID: 0372516 Medline TA: Biochem Biophys Res Commun Country: United States |
Other Details:
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Languages: eng Pagination: 309-17 Citation Subset: IM |
Affiliation:
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Department of Neurology, Juntendo University School of Medicine, 2-1-1 Hongo, Bunkyo-ku, Tokyo 113-8421, Japan. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Cell Line, Tumor Humans I-kappa B Proteins / analysis, metabolism* Lewy Bodies / chemistry, enzymology* Parkinson Disease / enzymology*, pathology Peptides / pharmacology Phosphorylation Protease Inhibitors / pharmacology Proteasome Endopeptidase Complex / antagonists & inhibitors SKP Cullin F-Box Protein Ligases / analysis Ubiquitin / analysis |
| Chemical | |
Reg. No./Substance:
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0/I-kappa B Proteins; 0/NBD peptide, mouse; 0/Peptides; 0/Protease Inhibitors; 0/Ubiquitin; 139874-52-5/NF-kappaB inhibitor alpha; EC 3.4.25.1/Proteasome Endopeptidase Complex; EC 6.3.2.19/SKP Cullin F-Box Protein Ligases |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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