Paraquat Induces Apoptosis in Human Lymphocytes : Protective and Rescue Effects of Glucose, Cannabinoids and Insulin-like Growth Factor-1

ABSTRACT In order to establish causal or protective treatments for Parkinson’s disease (PD), it is necessary to identify the cascade of deleterious events that lead to the dysfunction and death of dopaminergic neurons. Paraquat (PQ) is a pesticide used as xenobiotic compound to model PD. However, th...

Full description

Autores:
Jiménez del Río, Marlene
Vélez Pardo, Carlos Alberto
Tipo de recurso:
Article of investigation
Fecha de publicación:
2008
Institución:
Universidad de Antioquia
Repositorio:
Repositorio UdeA
Idioma:
eng
OAI Identifier:
oai:bibliotecadigital.udea.edu.co:10495/32453
Acceso en línea:
https://hdl.handle.net/10495/32453
https://www.tandfonline.com/doi/full/10.1080/08977190801984205
Palabra clave:
Apoptosis
Oxidative Stress
Estrés Oxidativo
NF-kappa B
FN-kappa B
Paraquat
Rights
openAccess
License
http://creativecommons.org/licenses/by-nc/2.5/co/
id UDEA2_858b8c41a4d3e6e28748bccb621d0eb5
oai_identifier_str oai:bibliotecadigital.udea.edu.co:10495/32453
network_acronym_str UDEA2
network_name_str Repositorio UdeA
repository_id_str
dc.title.spa.fl_str_mv Paraquat Induces Apoptosis in Human Lymphocytes : Protective and Rescue Effects of Glucose, Cannabinoids and Insulin-like Growth Factor-1
title Paraquat Induces Apoptosis in Human Lymphocytes : Protective and Rescue Effects of Glucose, Cannabinoids and Insulin-like Growth Factor-1
spellingShingle Paraquat Induces Apoptosis in Human Lymphocytes : Protective and Rescue Effects of Glucose, Cannabinoids and Insulin-like Growth Factor-1
Apoptosis
Oxidative Stress
Estrés Oxidativo
NF-kappa B
FN-kappa B
Paraquat
title_short Paraquat Induces Apoptosis in Human Lymphocytes : Protective and Rescue Effects of Glucose, Cannabinoids and Insulin-like Growth Factor-1
title_full Paraquat Induces Apoptosis in Human Lymphocytes : Protective and Rescue Effects of Glucose, Cannabinoids and Insulin-like Growth Factor-1
title_fullStr Paraquat Induces Apoptosis in Human Lymphocytes : Protective and Rescue Effects of Glucose, Cannabinoids and Insulin-like Growth Factor-1
title_full_unstemmed Paraquat Induces Apoptosis in Human Lymphocytes : Protective and Rescue Effects of Glucose, Cannabinoids and Insulin-like Growth Factor-1
title_sort Paraquat Induces Apoptosis in Human Lymphocytes : Protective and Rescue Effects of Glucose, Cannabinoids and Insulin-like Growth Factor-1
dc.creator.fl_str_mv Jiménez del Río, Marlene
Vélez Pardo, Carlos Alberto
dc.contributor.author.none.fl_str_mv Jiménez del Río, Marlene
Vélez Pardo, Carlos Alberto
dc.subject.decs.none.fl_str_mv Apoptosis
Oxidative Stress
Estrés Oxidativo
NF-kappa B
FN-kappa B
Paraquat
topic Apoptosis
Oxidative Stress
Estrés Oxidativo
NF-kappa B
FN-kappa B
Paraquat
description ABSTRACT In order to establish causal or protective treatments for Parkinson’s disease (PD), it is necessary to identify the cascade of deleterious events that lead to the dysfunction and death of dopaminergic neurons. Paraquat (PQ) is a pesticide used as xenobiotic compound to model PD. However, the mechanism(s) of PQ-induced cell death and the mechanism(s) of cytoprotection in a single cell model are still unknown. In this study, lymphocytes were treated with (0.1–1 mM) PQ. Apoptotic morphology was assessed with acridine orange/ethidium bromide staining. Further evaluation included (i) superoxide radicals, reflected by nitroblue tetrazolium reduction to formazan, (ii) the production of hydrogen peroxide, reflected by rhodamine-positive fluorescent cells, (iii) the generation of hydroxyl radicals, reflected by dimethylsulfoxide and melatonin z OH scavengers, (iv) activation and/or translocation of NF-kB, p53 and c-Jun transcription factors showed by immunocytochemical staining, and by ammonium pyrrolidinedithiocarbamate, pifithrin-a and SP600125 inhibition and (V) caspase-3 activation, reflected by caspase Ac-DEVD-cho inhibition. To elucidate the mechanism of cytoprotection, lymphocytes were treated with PQ in the presence of cannabinoids, insulin-like growth factor-1 and glucose. We provide evidence that PQ induces apoptosis in lymphocytes in a concentration- and time-dependent fashion by an oxidative stress mechanism involving O2 z2, H2O2/(z OH) generation, simultaneous activation of NF-kB/p53/c-Jun transcription factors, mitochondrial depolarization and caspase-3 activation leading to morphological apoptosis. Moreover, dying lymphocytes are protected and rescued from PQ noxious stimuli by direct antioxidant effect by cannabinoids, receptor mediated signaling by IGF-1, and/or energetic protection by glucose. It is concluded that PQ-induced apoptosis in lymphocytes by a mechanism involving reactive oxygen species generation, mitochondrial dysfunction, transcriptional factors and caspase-3 activation. However, this cell death routine can be reversed by the action of cannabinoids, IGF-1 and glucose. These data may provide innovating therapeutic strategies to intervene environmentally or genetically susceptible PD population to oxidative stress.
publishDate 2008
dc.date.issued.none.fl_str_mv 2008
dc.date.accessioned.none.fl_str_mv 2022-11-29T22:14:43Z
dc.date.available.none.fl_str_mv 2022-11-29T22:14:43Z
dc.type.spa.fl_str_mv info:eu-repo/semantics/article
dc.type.coarversion.fl_str_mv http://purl.org/coar/version/c_970fb48d4fbd8a85
dc.type.hasversion.spa.fl_str_mv info:eu-repo/semantics/publishedVersion
dc.type.coar.spa.fl_str_mv http://purl.org/coar/resource_type/c_2df8fbb1
dc.type.redcol.spa.fl_str_mv https://purl.org/redcol/resource_type/ART
dc.type.local.spa.fl_str_mv Artículo de investigación
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status_str publishedVersion
dc.identifier.issn.none.fl_str_mv 0897-7194
dc.identifier.uri.none.fl_str_mv https://hdl.handle.net/10495/32453
dc.identifier.doi.none.fl_str_mv 10.1080/08977190801984205
dc.identifier.eissn.none.fl_str_mv 1029-2292
dc.identifier.url.spa.fl_str_mv https://www.tandfonline.com/doi/full/10.1080/08977190801984205
identifier_str_mv 0897-7194
10.1080/08977190801984205
1029-2292
url https://hdl.handle.net/10495/32453
https://www.tandfonline.com/doi/full/10.1080/08977190801984205
dc.language.iso.spa.fl_str_mv eng
language eng
dc.relation.ispartofjournalabbrev.spa.fl_str_mv Growth Factors.
dc.rights.spa.fl_str_mv info:eu-repo/semantics/openAccess
dc.rights.uri.*.fl_str_mv http://creativecommons.org/licenses/by-nc/2.5/co/
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eu_rights_str_mv openAccess
rights_invalid_str_mv http://creativecommons.org/licenses/by-nc/2.5/co/
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dc.format.extent.spa.fl_str_mv 12
dc.format.mimetype.spa.fl_str_mv application/pdf
dc.publisher.spa.fl_str_mv Harwood Academic Publishers; Taylor and Francis
dc.publisher.group.spa.fl_str_mv Grupo de Neurociencias de Antioquia
dc.publisher.place.spa.fl_str_mv Yverdon-Les-Baibs, Suiza
institution Universidad de Antioquia
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spelling Jiménez del Río, MarleneVélez Pardo, Carlos Alberto2022-11-29T22:14:43Z2022-11-29T22:14:43Z20080897-7194https://hdl.handle.net/10495/3245310.1080/089771908019842051029-2292https://www.tandfonline.com/doi/full/10.1080/08977190801984205ABSTRACT In order to establish causal or protective treatments for Parkinson’s disease (PD), it is necessary to identify the cascade of deleterious events that lead to the dysfunction and death of dopaminergic neurons. Paraquat (PQ) is a pesticide used as xenobiotic compound to model PD. However, the mechanism(s) of PQ-induced cell death and the mechanism(s) of cytoprotection in a single cell model are still unknown. In this study, lymphocytes were treated with (0.1–1 mM) PQ. Apoptotic morphology was assessed with acridine orange/ethidium bromide staining. Further evaluation included (i) superoxide radicals, reflected by nitroblue tetrazolium reduction to formazan, (ii) the production of hydrogen peroxide, reflected by rhodamine-positive fluorescent cells, (iii) the generation of hydroxyl radicals, reflected by dimethylsulfoxide and melatonin z OH scavengers, (iv) activation and/or translocation of NF-kB, p53 and c-Jun transcription factors showed by immunocytochemical staining, and by ammonium pyrrolidinedithiocarbamate, pifithrin-a and SP600125 inhibition and (V) caspase-3 activation, reflected by caspase Ac-DEVD-cho inhibition. To elucidate the mechanism of cytoprotection, lymphocytes were treated with PQ in the presence of cannabinoids, insulin-like growth factor-1 and glucose. We provide evidence that PQ induces apoptosis in lymphocytes in a concentration- and time-dependent fashion by an oxidative stress mechanism involving O2 z2, H2O2/(z OH) generation, simultaneous activation of NF-kB/p53/c-Jun transcription factors, mitochondrial depolarization and caspase-3 activation leading to morphological apoptosis. Moreover, dying lymphocytes are protected and rescued from PQ noxious stimuli by direct antioxidant effect by cannabinoids, receptor mediated signaling by IGF-1, and/or energetic protection by glucose. It is concluded that PQ-induced apoptosis in lymphocytes by a mechanism involving reactive oxygen species generation, mitochondrial dysfunction, transcriptional factors and caspase-3 activation. However, this cell death routine can be reversed by the action of cannabinoids, IGF-1 and glucose. These data may provide innovating therapeutic strategies to intervene environmentally or genetically susceptible PD population to oxidative stress.COL001074412application/pdfengHarwood Academic Publishers; Taylor and FrancisGrupo de Neurociencias de AntioquiaYverdon-Les-Baibs, Suizainfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articlehttp://purl.org/coar/resource_type/c_2df8fbb1https://purl.org/redcol/resource_type/ARTArtículo de investigaciónhttp://purl.org/coar/version/c_970fb48d4fbd8a85info:eu-repo/semantics/openAccesshttp://creativecommons.org/licenses/by-nc/2.5/co/http://purl.org/coar/access_right/c_abf2https://creativecommons.org/licenses/by-nc/4.0/Paraquat Induces Apoptosis in Human Lymphocytes : Protective and Rescue Effects of Glucose, Cannabinoids and Insulin-like Growth Factor-1ApoptosisOxidative StressEstrés OxidativoNF-kappa BFN-kappa BParaquatGrowth Factors.Growth Factors4960261ORIGINALJimenezMarlene_2008_ParaquatInducesApoptosis.pdfJimenezMarlene_2008_ParaquatInducesApoptosis.pdfArtículo de investigaciónapplication/pdf3823554https://bibliotecadigital.udea.edu.co/bitstream/10495/32453/1/JimenezMarlene_2008_ParaquatInducesApoptosis.pdf4cc2cff3b7a26a929fdef8d464569dd0MD51CC-LICENSElicense_rdflicense_rdfapplication/rdf+xml; charset=utf-8933https://bibliotecadigital.udea.edu.co/bitstream/10495/32453/2/license_rdfc0c92b0ffc8b7d22d9cf56754a416a76MD52LICENSElicense.txtlicense.txttext/plain; charset=utf-81748https://bibliotecadigital.udea.edu.co/bitstream/10495/32453/3/license.txt8a4605be74aa9ea9d79846c1fba20a33MD5310495/32453oai:bibliotecadigital.udea.edu.co:10495/324532022-11-29 17:14:43.202Repositorio Institucional Universidad de Antioquiaandres.perez@udea.edu.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