Source:http://linkedlifedata.com/resource/pubmed/id/19835916
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rdf:type | |
lifeskim:mentions | |
pubmed:issue |
1
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pubmed:dateCreated |
2010-2-1
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pubmed:abstractText |
Parkinson's disease (PD) is a neurodegenerative disorder characterized by the selective loss of dopaminergic neurons and the presence of Lewy bodies. alpha-Synuclein is a major component of Lewy bodies. Recently, many studies have focused on the interaction between alpha-synuclein and catecholamine in the pathogenesis of PD. However, no detailed relationship between cathecholamine and alpha-synuclein cytotoxicity has been elucidated. Therefore, this study established PC12 cell lines which overexpress human alpha-synuclein in a tetracycline-inducible manner. The overexpression of human alpha-synuclein increased the number of apoptotic cells in a long-term culture. Moreover, human alpha-synuclein expressing PC12 cells demonstrated an increased vulnerability to several stressors in a short culture period. Thapsigargin increased the SDS soluble oligomers of alpha-synuclein associated with catecholamine-quinone. The unfolded protein response (UPR) study showed that thapsigargin increased eIF2alpha phosphorylation and nuclear GADD153/CHOP induction under alpha-synuclein overexpressed conditions. The activities of the ATF6alpha and IRE1alpha pathways decreased. These findings suggest that an overexpression of alpha-synuclein partly inactivates the UPR. alpha-Methyltyrosine inhibited the dysfunction of the UPR caused by an overexpression of human alpha-synuclein. Therefore, these findings suggest that the coexistence of human alpha-synuclein with catecholamine enhances the endoplasmic reticulum stress-related toxicity in PD pathogenesis.
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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/Catecholamines,
http://linkedlifedata.com/resource/pubmed/chemical/ELF2 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Enzyme Inhibitors,
http://linkedlifedata.com/resource/pubmed/chemical/Nerve Growth Factor,
http://linkedlifedata.com/resource/pubmed/chemical/Thapsigargin,
http://linkedlifedata.com/resource/pubmed/chemical/Transcription Factor CHOP,
http://linkedlifedata.com/resource/pubmed/chemical/Transcription Factors,
http://linkedlifedata.com/resource/pubmed/chemical/alpha-Methyltyrosine,
http://linkedlifedata.com/resource/pubmed/chemical/alpha-Synuclein,
http://linkedlifedata.com/resource/pubmed/chemical/beta-Synuclein
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pubmed:status |
MEDLINE
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pubmed:month |
Jan
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pubmed:issn |
1872-8111
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pubmed:author | |
pubmed:copyrightInfo |
Copyright 2009 Elsevier Ireland Ltd and the Japan Neuroscience Society. All rights reserved.
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pubmed:issnType |
Electronic
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pubmed:volume |
66
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
124-30
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pubmed:meshHeading |
pubmed-meshheading:19835916-Analysis of Variance,
pubmed-meshheading:19835916-Animals,
pubmed-meshheading:19835916-Apoptosis,
pubmed-meshheading:19835916-Catecholamines,
pubmed-meshheading:19835916-Enzyme Inhibitors,
pubmed-meshheading:19835916-Humans,
pubmed-meshheading:19835916-Immunoprecipitation,
pubmed-meshheading:19835916-Nerve Growth Factor,
pubmed-meshheading:19835916-PC12 Cells,
pubmed-meshheading:19835916-Phosphorylation,
pubmed-meshheading:19835916-Rats,
pubmed-meshheading:19835916-Thapsigargin,
pubmed-meshheading:19835916-Transcription Factor CHOP,
pubmed-meshheading:19835916-Transcription Factors,
pubmed-meshheading:19835916-Transfection,
pubmed-meshheading:19835916-Unfolded Protein Response,
pubmed-meshheading:19835916-alpha-Methyltyrosine,
pubmed-meshheading:19835916-alpha-Synuclein,
pubmed-meshheading:19835916-beta-Synuclein
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pubmed:year |
2010
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pubmed:articleTitle |
Endogenous catecholamine enhances the dysfunction of unfolded protein response and alpha-synuclein oligomerization in PC12 cells overexpressing human alpha-synuclein.
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pubmed:affiliation |
Department of Neurology, Institute of Neurological Sciences, Faculty of Medicine, Tottori University, Japan. s-itou@med.tottori-u.ac.jp
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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