Linked Life Data

19835916

Source:http://linkedlifedata.com/resource/pubmed/id/19835916

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
1
pubmed:dateCreated
2010-2-1
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.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jan
pubmed:issn
1872-8111
pubmed:author
pubmed:copyrightInfo
Copyright 2009 Elsevier Ireland Ltd and the Japan Neuroscience Society. All rights reserved.
pubmed:issnType
Electronic
pubmed:volume
66
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
124-30
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
pubmed:year
2010
pubmed:articleTitle
Endogenous catecholamine enhances the dysfunction of unfolded protein response and alpha-synuclein oligomerization in PC12 cells overexpressing human alpha-synuclein.
pubmed:affiliation
Department of Neurology, Institute of Neurological Sciences, Faculty of Medicine, Tottori University, Japan. s-itou@med.tottori-u.ac.jp
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't