Protection against neurotoxicity by an autophagic mechanism

Detalhes bibliográficos
Autor(a) principal: Liu,Kangyong
Data de Publicação: 2012
Outros Autores: Huang,Jiankang, Chen,Rongfu, Zhang,Ting, Shen,Liwei, Yang,Jiajun, Sun,Xiaojiang
Tipo de documento: Artigo
Idioma: eng
Título da fonte: Brazilian Journal of Medical and Biological Research
Texto Completo: http://old.scielo.br/scielo.php?script=sci_arttext&pid=S0100-879X2012000500004
Resumo: The objective of the present study was to investigate the effects of 3-n-butylphthalide (NBP) on a 1-methyl-4-phenylpyridinium (MPP+)-induced cellular model of Parkinson’s disease (PD) and to illustrate the potential mechanism of autophagy in this process. For this purpose, rat PC12 pheochromocytoma cells were treated with MPP+ (1 mM) for 24 h following pretreatment with NBP (0.1 mM). Cell metabolic viability was determined by the MTT assay and cell ultrastructure was examined by transmission electron microscopy. The intracellular distribution and expression of α-synuclein and microtubule-associated protein light chain 3 (LC3) were detected by immunocytochemistry and Western blotting. Our results demonstrated that: 1) NBP prevented MPP+-induced cytotoxicity in PC12 cells by promoting metabolic viability. 2) NBP induced the accumulation of autophagosomes in MPP+-treated PC12 cells. 3) Further study of the molecular mechanism demonstrated that NBP enhanced the colocalization of α-synuclein and LC3 and up-regulated the protein level of LC3-II. These results demonstrate that NBP protects PC12 cells against MPP+-induced neurotoxicity by activating autophagy-mediated α-synuclein degradation, implying that it may be a potential effective therapeutic agent for the treatment of PD.
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spelling Protection against neurotoxicity by an autophagic mechanism3-N-butylphthalideParkinson’s diseaseα-synucleinPC12 cellsAutophagyThe objective of the present study was to investigate the effects of 3-n-butylphthalide (NBP) on a 1-methyl-4-phenylpyridinium (MPP+)-induced cellular model of Parkinson’s disease (PD) and to illustrate the potential mechanism of autophagy in this process. For this purpose, rat PC12 pheochromocytoma cells were treated with MPP+ (1 mM) for 24 h following pretreatment with NBP (0.1 mM). Cell metabolic viability was determined by the MTT assay and cell ultrastructure was examined by transmission electron microscopy. The intracellular distribution and expression of α-synuclein and microtubule-associated protein light chain 3 (LC3) were detected by immunocytochemistry and Western blotting. Our results demonstrated that: 1) NBP prevented MPP+-induced cytotoxicity in PC12 cells by promoting metabolic viability. 2) NBP induced the accumulation of autophagosomes in MPP+-treated PC12 cells. 3) Further study of the molecular mechanism demonstrated that NBP enhanced the colocalization of α-synuclein and LC3 and up-regulated the protein level of LC3-II. These results demonstrate that NBP protects PC12 cells against MPP+-induced neurotoxicity by activating autophagy-mediated α-synuclein degradation, implying that it may be a potential effective therapeutic agent for the treatment of PD.Associação Brasileira de Divulgação Científica2012-05-01info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersiontext/htmlhttp://old.scielo.br/scielo.php?script=sci_arttext&pid=S0100-879X2012000500004Brazilian Journal of Medical and Biological Research v.45 n.5 2012reponame:Brazilian Journal of Medical and Biological Researchinstname:Associação Brasileira de Divulgação Científica (ABDC)instacron:ABDC10.1590/S0100-879X2012007500039info:eu-repo/semantics/openAccessLiu,KangyongHuang,JiankangChen,RongfuZhang,TingShen,LiweiYang,JiajunSun,Xiaojiangeng2012-05-04T00:00:00Zoai:scielo:S0100-879X2012000500004Revistahttps://www.bjournal.org/https://old.scielo.br/oai/scielo-oai.phpbjournal@terra.com.br||bjournal@terra.com.br1414-431X0100-879Xopendoar:2012-05-04T00:00Brazilian Journal of Medical and Biological Research - Associação Brasileira de Divulgação Científica (ABDC)false
dc.title.none.fl_str_mv Protection against neurotoxicity by an autophagic mechanism
title Protection against neurotoxicity by an autophagic mechanism
spellingShingle Protection against neurotoxicity by an autophagic mechanism
Liu,Kangyong
3-N-butylphthalide
Parkinson’s disease
α-synuclein
PC12 cells
Autophagy
title_short Protection against neurotoxicity by an autophagic mechanism
title_full Protection against neurotoxicity by an autophagic mechanism
title_fullStr Protection against neurotoxicity by an autophagic mechanism
title_full_unstemmed Protection against neurotoxicity by an autophagic mechanism
title_sort Protection against neurotoxicity by an autophagic mechanism
author Liu,Kangyong
author_facet Liu,Kangyong
Huang,Jiankang
Chen,Rongfu
Zhang,Ting
Shen,Liwei
Yang,Jiajun
Sun,Xiaojiang
author_role author
author2 Huang,Jiankang
Chen,Rongfu
Zhang,Ting
Shen,Liwei
Yang,Jiajun
Sun,Xiaojiang
author2_role author
author
author
author
author
author
dc.contributor.author.fl_str_mv Liu,Kangyong
Huang,Jiankang
Chen,Rongfu
Zhang,Ting
Shen,Liwei
Yang,Jiajun
Sun,Xiaojiang
dc.subject.por.fl_str_mv 3-N-butylphthalide
Parkinson’s disease
α-synuclein
PC12 cells
Autophagy
topic 3-N-butylphthalide
Parkinson’s disease
α-synuclein
PC12 cells
Autophagy
description The objective of the present study was to investigate the effects of 3-n-butylphthalide (NBP) on a 1-methyl-4-phenylpyridinium (MPP+)-induced cellular model of Parkinson’s disease (PD) and to illustrate the potential mechanism of autophagy in this process. For this purpose, rat PC12 pheochromocytoma cells were treated with MPP+ (1 mM) for 24 h following pretreatment with NBP (0.1 mM). Cell metabolic viability was determined by the MTT assay and cell ultrastructure was examined by transmission electron microscopy. The intracellular distribution and expression of α-synuclein and microtubule-associated protein light chain 3 (LC3) were detected by immunocytochemistry and Western blotting. Our results demonstrated that: 1) NBP prevented MPP+-induced cytotoxicity in PC12 cells by promoting metabolic viability. 2) NBP induced the accumulation of autophagosomes in MPP+-treated PC12 cells. 3) Further study of the molecular mechanism demonstrated that NBP enhanced the colocalization of α-synuclein and LC3 and up-regulated the protein level of LC3-II. These results demonstrate that NBP protects PC12 cells against MPP+-induced neurotoxicity by activating autophagy-mediated α-synuclein degradation, implying that it may be a potential effective therapeutic agent for the treatment of PD.
publishDate 2012
dc.date.none.fl_str_mv 2012-05-01
dc.type.driver.fl_str_mv info:eu-repo/semantics/article
dc.type.status.fl_str_mv info:eu-repo/semantics/publishedVersion
format article
status_str publishedVersion
dc.identifier.uri.fl_str_mv http://old.scielo.br/scielo.php?script=sci_arttext&pid=S0100-879X2012000500004
url http://old.scielo.br/scielo.php?script=sci_arttext&pid=S0100-879X2012000500004
dc.language.iso.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv 10.1590/S0100-879X2012007500039
dc.rights.driver.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv text/html
dc.publisher.none.fl_str_mv Associação Brasileira de Divulgação Científica
publisher.none.fl_str_mv Associação Brasileira de Divulgação Científica
dc.source.none.fl_str_mv Brazilian Journal of Medical and Biological Research v.45 n.5 2012
reponame:Brazilian Journal of Medical and Biological Research
instname:Associação Brasileira de Divulgação Científica (ABDC)
instacron:ABDC
instname_str Associação Brasileira de Divulgação Científica (ABDC)
instacron_str ABDC
institution ABDC
reponame_str Brazilian Journal of Medical and Biological Research
collection Brazilian Journal of Medical and Biological Research
repository.name.fl_str_mv Brazilian Journal of Medical and Biological Research - Associação Brasileira de Divulgação Científica (ABDC)
repository.mail.fl_str_mv bjournal@terra.com.br||bjournal@terra.com.br
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