3 252

Cited 298 times in

Aggresomes formed by alpha-synuclein and synphilin-1 are cytoprotective.

Authors
Tanaka, M; Kim, YM; Lee, G; Junn, E; Iwatsubo, T; Mouradian, MM
Citation
The Journal of biological chemistry, 279(6):4625-4631, 2004
Journal Title
The Journal of biological chemistry
ISSN
0021-92581083-351X
Abstract
Lewy bodies (LBs), which are the hallmark pathologic features of Parkinson's disease and of dementia with LBs, have several morphologic and molecular similarities to aggresomes. Whether such cytoplasmic inclusions contribute to neuronal death or protect cells from the toxic effects of misfolded proteins remains controversial. In this report, the role of aggresomes in cell viability was addressed in the context of over-expressing alpha-synuclein and its interacting partner synphilin-1 using engineered 293T cells. Inhibition of proteasome activity elicited the formation of juxtanuclear aggregates with characteristics of aggresomes including immunoreactivity for vimentin, gamma-tubulin, ubiquitin, proteasome subunit, and hsp70. As expected from the properties of aggresomes, the microtubule disrupting agents, vinblastin and nocodazole, markedly prevented the formation of these inclusions. Similar to LBs, the phosphorylated form of alpha-synuclein co-localized in these synphilin-1-containing aggresomes. Although the caspase inhibitor z-VAD-fmk significantly reduced the number of apoptotic cells, it had no impact on the percentage of aggresome-positive cells. Finally, quantitative analysis revealed aggresomes in 60% of nonapoptotic cells but only in 10% of apoptotic cells. Additionally, alpha-synuclein-induced apoptosis was not coupled with increased prevalence of aggresome-bearing cells. Taken together, these observations indicate a disconnection between aggresome formation and apoptosis, and support a protective role for these inclusions from the toxicity associated with the combined over-expression of alpha-synuclein and synphilin-1.
MeSH terms
Amino Acid Chloromethyl Ketones/pharmacologyApoptosis/drug effects/physiologyCarrier Proteins/*chemistry/genetics/*metabolismCell LineCell SurvivalCysteine Proteinase Inhibitors/pharmacologyHumansInclusion Bodies/drug effects/*metabolismLewy Bodies/metabolismLewy Body Disease/metabolism/pathologyMacromolecular SubstancesMicrotubules/drug effectsNerve Tissue Proteins/*chemistry/genetics/*metabolismNeurons/drug effects/metabolism/pathologyNeuroprotective Agents/pharmacologyNocodazole/pharmacologyParkinson Disease/metabolism/pathologyRecombinant Proteins/chemistry/genetics/metabolismSynucleinsTransfectionVinblastine/pharmacologyalpha-Synuclein
DOI
10.1074/jbc.M310994200
PMID
14627698
Appears in Collections:
Journal Papers > School of Medicine / Graduate School of Medicine > Physiology
AJOU Authors
이, 광
Full Text Link
Export
RIS (EndNote)
XLS (Excel)
XML

qrcode

해당 아이템을 이메일로 공유하기 원하시면 인증을 거치시기 바랍니다.

Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.

Browse